转铁蛋白修饰的CPT-PAMAM-PEG复合物的肿瘤靶向研究
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摘要
恶性肿瘤已经成为威胁人类健康和生命的最主要疾病之一,其发病率每年新增近1千万例。近几年对肿瘤生理深入的探索,促进了肿瘤诊断和治疗的发展,其死亡率有所下降。目前肿瘤的治疗手段包括手术治疗,放疗和化疗等,放化疗在杀死肿瘤细胞的同时也能杀死正常细胞,给病人带来严重的毒副作用。因此研制更有效地靶向肿瘤细胞的给药系统显得尤为迫切。被动靶向释药系统成功利用肿瘤的生理特征使载药系统通过EPR效应在肿瘤部位蓄积。药物聚合物纳米载体系统由于其良好的可调控性、易于表面修饰、较高的药物包封率、较强的药物保护作用和适于大规模生产,已成为研究热点之一。虽然被动靶向释药奠定了靶向给药临床治疗的基础,但仍存在难以克服一些问题,如并不是所有的肿瘤都能体现出EPR效应,肿瘤细胞的多药耐药现象使部分药物不能有效地进入肿瘤细胞等等。要克服这些困难,则需要使载药系统主动地靶向肿瘤细胞,主动靶向可以通过与细胞表面特定的受体相结合的配体或抗体来实现。
本课题通过药剂学、高分子材料学、药理学、分子生物学等手段的交叉应用,以喜树碱(CPT)为模型药物,转铁蛋白(Tf)为靶向头基,首先制备载CPT的主动靶向隐形纳米载药系统,将聚乙二醇(PEG)修饰的被动靶向与Tf修饰的主动靶向作用相结合,有效递送药物到达肿瘤部位。
本课题以琥珀酸酐为连接剂,首先合成了琥珀酰喜树碱酯,并用N-羟基琥珀酰亚胺(NHS)活化。用带有双功能基团的NHS-PEG-MAL分子上的NHS端与PAMAM上的氨基相连,合成了三种不同PEG化程度的PAMAM-PEG(PP_(16),PP_(32)和PP_(48)),通过~1H NMR计算PAMAM所连接的PEG数量并测定了粒径和Zeta电位。喜树碱琥珀酸活化酯与PAMAM表面剩余的氨基共价连接,合成了CPT-PAMAM-PEG纳米载药系统(CPP_(16),CPP_(32)和CPP_(48))。药物的体外释放显示出缓释的特性(120小时内累积释放75%)。用Traut's试剂将转铁蛋白巯基化,合成了转铁蛋白修饰的主动靶向载药纳米复合物CPT-PAMAM-PEG-Tf(CPP_(16)T,CPP_(32)T和CPP_(48)T),采用bradford法测得平均每个PAMAM复合物连接1分子转铁蛋白。连接转铁蛋白后复合物的粒径增加了近一倍,Zeta电位由正负。转铁蛋白修饰的CPT复合物较CPT原料药和未经转铁蛋白修饰的复合物对KB,K562和S180细胞显示出更强的抗肿瘤活性。细胞摄取实验显示转铁蛋白修饰的PAMAM-PEG复合物在KB、K562细胞中的摄取量分别为未经Tf修饰复合物的3.38～3.46倍和2.52～2.86倍。实验显示转铁蛋白修饰的PAMAM-PEG复合物在KB细胞中的摄取具有浓度依赖性,且转铁蛋白可以明显抑制复合物的摄取,说明其通过细胞表面高表达的转铁蛋白受体介导的内吞进入细胞。
以异硫氰酸罗丹明B(RBITC)为荧光标记物,合成了带荧光标记物的RPP和RPPT。采用各种内吞抑制剂对复合物的内吞机制进行了初步探讨,结果显示RPP_(48)和RPP_(48)T都是由细胞表面的网格蛋白介导内吞,RPP_(48)T以细胞表面的转铁蛋白受体介导的内吞为主。用Lysotracker green对细胞溶酶体进行染色,激光共聚集显微镜观察表明复合物内吞后经溶酶体途径转运。
采用Hochest和PI双染对低浓度CPT复合物诱导肿瘤细胞凋亡的研究发现,CPT,CPP_(48)和CPP_(48)T 12h诱导细胞早期凋亡率分别为0.76%,2.41%和4.63%,24h分别为4.75%,16.02%和30.91%。说明CPP_(48)T被肿瘤细胞摄取最多,诱导凋亡的效果最好。
大鼠体内药动学显示复合物中PEG化程度越大,复合物在体内的半衰期和平均滞留时间越长,AUC也越大,但是经转铁蛋白修饰的复合物较未经Tf修饰的复合物的半衰期短。S180荷瘤小鼠体内的组织分布结果表明CPP_(48)T给药后药物在肿瘤内的达峰浓度最高,分别是CPT和CPP_(48)的8.4和2.7倍,AUC分别是CPT和CPP_(48)的28.7和3.6倍。CPP_(48)T的相对靶向效率最高(28.7),显示CPP_(48)T的肿瘤靶向性最强。
对S-180荷瘤小鼠的药效研究结果表明,CPP_(48)T具有最强的抗肿瘤活性,其肿瘤抑制率为65.7%,分别是CPT和CPP_(48)的1.81和1.27倍,显出主动靶向与被动靶向相合的优势。荷瘤小鼠的体重变化和小鼠小肠的组织病理切片显示其没有明显的毒副作用。肿瘤组织切片免疫组化结果显示,CPP_(48)T肿瘤细胞增殖最少,细胞凋亡最明显,表明CPP_(48)T具有最强的抗肿瘤活性。
Cancer remains one of the world's most devastating diseases,with more than 10 million new cased very year.However,mortality has decreased in the past two years, owing to better understanding of tumor biology and improved diagnostic devices and treatments.Current cancer treatments include surgical intervention,radiation and chemotherapeutic drugs,which often also kill healthy cells and cause toxicity to the patient.It would therefore be desirable to develop chemotherapeutics that can either passively or actively target cancerous cells.Passive targeting exploits the characteristic features of tumor biology that allow nanocarriers to accumulate in the tumor by the enhanced permeability and retention(EPR) effect.Polymeric drug delivery system has been one of the hot research fields not only because of its tremendous versatility in polymer matrices allowing for tailoring of the system properties to meet the specific intended need,but also its ease of surface modification, high encapsulation efficiency of the drug,drug protection,control over the release of drugs,and feasibility of scale-up and manufacturing.Although passive targeting approaches form the basis of clinical therapy,they suffer from several limitation because certain tumor do not exhibit the EPR effect and some drugs cannot diffuse efficiently for multiple-drug resistance.One way to overcome these limitations is to programme the nanocarrers so they actively bind to specific cells.This binding cay be achieved by attaching targeting agents such as ligands molecules that bind go specific receptors on the cell surface.
In this study,by means of pharmaceutics,macromolecular chemistry, pharmacology and molecular biology,CPT loaded transferrin modified PEG-PAMAM dendrimers were first prepared for effective drug delivery to solid tomor by the combination of passive and active targeting.
succinic anhydride as linker,We first synthezised Camptothecin-hemisuccinate. The remain carboxyl group was activated by N-Hydroxysuccinimide.The primary amino groups on the surface of PAMAM were specifically reacted with the NHS groups of the bifunctional PEG derivative.Three different PEG proportion conjugates PP_(16),PP_(32) and PP_(48) were obtained and the average number of PEG chains attached PAMAM were 10.5,20.2 and 28.8 calculated through ~1H NMR spectra.The average diameters of three conjugates were 7.12nm,7.34nm and 8.56nm,respectively and the Zeta potential were 4.84mV,4.43mV and 1.90mV.Camptothecin-SA-NHS ester were reacted with the remains amino groups on the surface of PAMAM,named CPP_(16), CPP_(32) and CPP_(48).The diameter and Zeta potential were also measured by Zetasizer Nano.The release profile of CPT from conjugates showed a slower and sustained fashion(75%of CPT was released within 120 h).Tf was thiolated using Traut's reagent and the extent of thiolation was determined by Ellmann's reagent.The MAL groups of PEG were specifically reacted with the thiol groups of thiolated Tf.The average number of Tf per conjugate was about 1.0 using Braford method.The diameter of CPP_(16)T,CPP_(32)T and CPP_(48)T were lager about 1-fold and the Zeta potential became negative.
Tf modified CPT-conjugates displayed the stronger tumor cell cytotoxicity compared with CPT solution and no Tf modified CPT-conjugates in KB,K562 and S180 cells.The mean fluorescence intensity were determined during flow mytometric analysis of the cellular uptake of conjugates against KB cell,K562 cells and S180 cells.The uptake of Tf modified CPT-conjugates were 3.38～3.46 fold in KB cells and 2.52～2.86 fold in K562 cells compared with no Tf modified CPT-conjugates.The uptake of conjugates by KB cells was concentration dependent,which could be inhibited by excess free Tf in the medium,strongly indicating that the uptake mechanism being an energy-driven,transferrin receptor mediated endocytosis process.
The endocytosis mechanism of Tf modified conjugates were evaluated.The results of cellular inhibition showed that CPP_(48) and CPP_(48)T could be taked up by KB cells via clathrin -dependent endocytosis.CPP_(48)T was major mediated via transferrin receptor and Lysosome apparatus were involvement in the cellular distribution.KB cells were incubated with rhodamine labeled conjugates in the presence of lysotracker green,a marker for secondary endosomes and lysosomes,colocalization of rhodamine labeled conjugates in late endosome and lysosome were observed,indicating that cellular transport of conjugate depends on the lysosome process.
To measure the apoptosis effect of CPT and conjugates quantificationally, Hochst33342 and PI was used to double stain KB cells.When cells were treated with CPT or conjugates with 1Nm for 12h,the early apoptosis of CPT,CPP_(48) and CPP_(48)T were 0.76%,2.41%and 4.63%,4.75%,16.02%and 30.91%for 24h,respectively, which was consistent with the above results and indicated that CPP_(48)T induce more apoptosis due to more uptake of CPT,and produce higher cytotoxicity than CPP_(48) and CPT.
The pharmacokinetic study in rats showed that The more PEG chains on surface of the conjugates,the longer t_(1/2) of the CPT were observed.However,the half life of conjugates became shorter than that of Tf modified conjugates.
The tissue distribution was investigated on S180 tumor bearing mice.CPP_(48)T showed the highest tumor concentration(8.4-fold and 2.7-fold that of CPT solution and CPP_(48),respectively),largest AUC in tumor(28.7-fold and 3.6-fold that of CPT solution and CPP_(48),respectively).Good tumor targeting effect of CPP48T was showed by the parameters.Relative targeting efficiency(r_e) was 28.7
CPP_(48)T showed the most powerful anti-tumor activity of with the inhibition rate of 65.7%against S180 tumor in mice(1.81-and 1.27-fold that of CPT solution and, respectively),which was attributed to the double effect from passive and active targeting.No significant side effects were observed by weight changes of the mice and the histological examination of the small intestine.Immunohistochemistry of the tumor tissues showed that CPP_(48)T had highest antitumor effects(inhibiting the tumor cells proliferation and inducing the tumor cells apoptosis).
本课题通过药剂学、高分子材料学、药理学、分子生物学等手段的交叉应用,以喜树碱(CPT)为模型药物,转铁蛋白(Tf)为靶向头基,首先制备载CPT的主动靶向隐形纳米载药系统,将聚乙二醇(PEG)修饰的被动靶向与Tf修饰的主动靶向作用相结合,有效递送药物到达肿瘤部位。
本课题以琥珀酸酐为连接剂,首先合成了琥珀酰喜树碱酯,并用N-羟基琥珀酰亚胺(NHS)活化。用带有双功能基团的NHS-PEG-MAL分子上的NHS端与PAMAM上的氨基相连,合成了三种不同PEG化程度的PAMAM-PEG(PP_(16),PP_(32)和PP_(48)),通过~1H NMR计算PAMAM所连接的PEG数量并测定了粒径和Zeta电位。喜树碱琥珀酸活化酯与PAMAM表面剩余的氨基共价连接,合成了CPT-PAMAM-PEG纳米载药系统(CPP_(16),CPP_(32)和CPP_(48))。药物的体外释放显示出缓释的特性(120小时内累积释放75%)。用Traut's试剂将转铁蛋白巯基化,合成了转铁蛋白修饰的主动靶向载药纳米复合物CPT-PAMAM-PEG-Tf(CPP_(16)T,CPP_(32)T和CPP_(48)T),采用bradford法测得平均每个PAMAM复合物连接1分子转铁蛋白。连接转铁蛋白后复合物的粒径增加了近一倍,Zeta电位由正负。转铁蛋白修饰的CPT复合物较CPT原料药和未经转铁蛋白修饰的复合物对KB,K562和S180细胞显示出更强的抗肿瘤活性。细胞摄取实验显示转铁蛋白修饰的PAMAM-PEG复合物在KB、K562细胞中的摄取量分别为未经Tf修饰复合物的3.38～3.46倍和2.52～2.86倍。实验显示转铁蛋白修饰的PAMAM-PEG复合物在KB细胞中的摄取具有浓度依赖性,且转铁蛋白可以明显抑制复合物的摄取,说明其通过细胞表面高表达的转铁蛋白受体介导的内吞进入细胞。
以异硫氰酸罗丹明B(RBITC)为荧光标记物,合成了带荧光标记物的RPP和RPPT。采用各种内吞抑制剂对复合物的内吞机制进行了初步探讨,结果显示RPP_(48)和RPP_(48)T都是由细胞表面的网格蛋白介导内吞,RPP_(48)T以细胞表面的转铁蛋白受体介导的内吞为主。用Lysotracker green对细胞溶酶体进行染色,激光共聚集显微镜观察表明复合物内吞后经溶酶体途径转运。
采用Hochest和PI双染对低浓度CPT复合物诱导肿瘤细胞凋亡的研究发现,CPT,CPP_(48)和CPP_(48)T 12h诱导细胞早期凋亡率分别为0.76%,2.41%和4.63%,24h分别为4.75%,16.02%和30.91%。说明CPP_(48)T被肿瘤细胞摄取最多,诱导凋亡的效果最好。
大鼠体内药动学显示复合物中PEG化程度越大,复合物在体内的半衰期和平均滞留时间越长,AUC也越大,但是经转铁蛋白修饰的复合物较未经Tf修饰的复合物的半衰期短。S180荷瘤小鼠体内的组织分布结果表明CPP_(48)T给药后药物在肿瘤内的达峰浓度最高,分别是CPT和CPP_(48)的8.4和2.7倍,AUC分别是CPT和CPP_(48)的28.7和3.6倍。CPP_(48)T的相对靶向效率最高(28.7),显示CPP_(48)T的肿瘤靶向性最强。
对S-180荷瘤小鼠的药效研究结果表明,CPP_(48)T具有最强的抗肿瘤活性,其肿瘤抑制率为65.7%,分别是CPT和CPP_(48)的1.81和1.27倍,显出主动靶向与被动靶向相合的优势。荷瘤小鼠的体重变化和小鼠小肠的组织病理切片显示其没有明显的毒副作用。肿瘤组织切片免疫组化结果显示,CPP_(48)T肿瘤细胞增殖最少,细胞凋亡最明显,表明CPP_(48)T具有最强的抗肿瘤活性。
Cancer remains one of the world's most devastating diseases,with more than 10 million new cased very year.However,mortality has decreased in the past two years, owing to better understanding of tumor biology and improved diagnostic devices and treatments.Current cancer treatments include surgical intervention,radiation and chemotherapeutic drugs,which often also kill healthy cells and cause toxicity to the patient.It would therefore be desirable to develop chemotherapeutics that can either passively or actively target cancerous cells.Passive targeting exploits the characteristic features of tumor biology that allow nanocarriers to accumulate in the tumor by the enhanced permeability and retention(EPR) effect.Polymeric drug delivery system has been one of the hot research fields not only because of its tremendous versatility in polymer matrices allowing for tailoring of the system properties to meet the specific intended need,but also its ease of surface modification, high encapsulation efficiency of the drug,drug protection,control over the release of drugs,and feasibility of scale-up and manufacturing.Although passive targeting approaches form the basis of clinical therapy,they suffer from several limitation because certain tumor do not exhibit the EPR effect and some drugs cannot diffuse efficiently for multiple-drug resistance.One way to overcome these limitations is to programme the nanocarrers so they actively bind to specific cells.This binding cay be achieved by attaching targeting agents such as ligands molecules that bind go specific receptors on the cell surface.
In this study,by means of pharmaceutics,macromolecular chemistry, pharmacology and molecular biology,CPT loaded transferrin modified PEG-PAMAM dendrimers were first prepared for effective drug delivery to solid tomor by the combination of passive and active targeting.
succinic anhydride as linker,We first synthezised Camptothecin-hemisuccinate. The remain carboxyl group was activated by N-Hydroxysuccinimide.The primary amino groups on the surface of PAMAM were specifically reacted with the NHS groups of the bifunctional PEG derivative.Three different PEG proportion conjugates PP_(16),PP_(32) and PP_(48) were obtained and the average number of PEG chains attached PAMAM were 10.5,20.2 and 28.8 calculated through ~1H NMR spectra.The average diameters of three conjugates were 7.12nm,7.34nm and 8.56nm,respectively and the Zeta potential were 4.84mV,4.43mV and 1.90mV.Camptothecin-SA-NHS ester were reacted with the remains amino groups on the surface of PAMAM,named CPP_(16), CPP_(32) and CPP_(48).The diameter and Zeta potential were also measured by Zetasizer Nano.The release profile of CPT from conjugates showed a slower and sustained fashion(75%of CPT was released within 120 h).Tf was thiolated using Traut's reagent and the extent of thiolation was determined by Ellmann's reagent.The MAL groups of PEG were specifically reacted with the thiol groups of thiolated Tf.The average number of Tf per conjugate was about 1.0 using Braford method.The diameter of CPP_(16)T,CPP_(32)T and CPP_(48)T were lager about 1-fold and the Zeta potential became negative.
Tf modified CPT-conjugates displayed the stronger tumor cell cytotoxicity compared with CPT solution and no Tf modified CPT-conjugates in KB,K562 and S180 cells.The mean fluorescence intensity were determined during flow mytometric analysis of the cellular uptake of conjugates against KB cell,K562 cells and S180 cells.The uptake of Tf modified CPT-conjugates were 3.38～3.46 fold in KB cells and 2.52～2.86 fold in K562 cells compared with no Tf modified CPT-conjugates.The uptake of conjugates by KB cells was concentration dependent,which could be inhibited by excess free Tf in the medium,strongly indicating that the uptake mechanism being an energy-driven,transferrin receptor mediated endocytosis process.
The endocytosis mechanism of Tf modified conjugates were evaluated.The results of cellular inhibition showed that CPP_(48) and CPP_(48)T could be taked up by KB cells via clathrin -dependent endocytosis.CPP_(48)T was major mediated via transferrin receptor and Lysosome apparatus were involvement in the cellular distribution.KB cells were incubated with rhodamine labeled conjugates in the presence of lysotracker green,a marker for secondary endosomes and lysosomes,colocalization of rhodamine labeled conjugates in late endosome and lysosome were observed,indicating that cellular transport of conjugate depends on the lysosome process.
To measure the apoptosis effect of CPT and conjugates quantificationally, Hochst33342 and PI was used to double stain KB cells.When cells were treated with CPT or conjugates with 1Nm for 12h,the early apoptosis of CPT,CPP_(48) and CPP_(48)T were 0.76%,2.41%and 4.63%,4.75%,16.02%and 30.91%for 24h,respectively, which was consistent with the above results and indicated that CPP_(48)T induce more apoptosis due to more uptake of CPT,and produce higher cytotoxicity than CPP_(48) and CPT.
The pharmacokinetic study in rats showed that The more PEG chains on surface of the conjugates,the longer t_(1/2) of the CPT were observed.However,the half life of conjugates became shorter than that of Tf modified conjugates.
The tissue distribution was investigated on S180 tumor bearing mice.CPP_(48)T showed the highest tumor concentration(8.4-fold and 2.7-fold that of CPT solution and CPP_(48),respectively),largest AUC in tumor(28.7-fold and 3.6-fold that of CPT solution and CPP_(48),respectively).Good tumor targeting effect of CPP48T was showed by the parameters.Relative targeting efficiency(r_e) was 28.7
CPP_(48)T showed the most powerful anti-tumor activity of with the inhibition rate of 65.7%against S180 tumor in mice(1.81-and 1.27-fold that of CPT solution and, respectively),which was attributed to the double effect from passive and active targeting.No significant side effects were observed by weight changes of the mice and the histological examination of the small intestine.Immunohistochemistry of the tumor tissues showed that CPP_(48)T had highest antitumor effects(inhibiting the tumor cells proliferation and inducing the tumor cells apoptosis).
引文
[1]国信证卷/医药行业/行业深度研究报告2008年
[2]Maeda H.The enhanced permeability and retention(EPR) effect in tumor vasculature:the key role of tumor-selective macromolecular drug targeting [J].Adv Enzyme Regul,2001,41(1):189-207.
[3]Maeda H,Wu J,Sawa T,et al.Tumor vascular permeability and the EPR effect in macromolecular therapeutics:a review[J].J Control Release,2000,65(1-2):271-284.
[4]Maeda H,Sawa T,Konno T.Mechanism of tumor-targeted delivery of macromolecular drugs,including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS[J].J Control Release,2001,74(1-3):47-61.
[5]Tanaka T,Shiramoto S,Miyashita M,et al.Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].Int J Pharm,2004,277(1-2):39-61.
[6]Greenwald RB.PEG drugs:an overview[J].J Control Release,2001,74(1-3):159-171.
[7]van Vlerken LE,Vyas TK,Amiji MM.Poly(ethylene glycol)-modified Nanocarriers for Tumor-targeted and Intracellular Delivery[J].Pharma Res,2007,24(8):1405-1414.
[8]Stolnik S,Illum L,Davis SS.Long circulating microparticulate drug carriers [J].Adv Drug Deliv Rev,1995,16(2-3):195-214.
[9]Redhead HM,Davis SS,Illum L.Drug delivery in poly(lactide-co-glycolide)nanoparticles surface modified with poloxamer 407 and poloxamine 908:in vitro characterisation and in vivo evaluation[J].J Control Release,2001,70(3):353-363.
[10]Zhang Y,Kohler N,Zhang M.Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake[J].Biomaterials,2002,23(7):1553-1561.
[11]Gref R,L(u|¨)ck M,Quellec P,et al.'Stealth' corona-core nanoparticles surface modified by polyethylene glycol(PEG):influences of the corona(PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption[J].Colloids Surf B Biointerfaces,2000,18(3-4):301-313.
[12] Sheng Y, Liu C, Yuan Y,et al. Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan[J].Biomaterials, 2009, 30(12):2340-2348.
[13] Li YP, Zhou ZH, Pei YY, et al. PEGylated polycyanoacrylate nanoparticles as salvicine carriers: synthesis, preparation, and in vitro characterization [J].Acta Pharmacol Sin, 2001, 22(7):645-650.
[14] Stolnik S, Daudali B, Arien A, et al. The effect of surface coverage and conformation of poly (ethylene oxide) (PEO) chains of poloxamer 407 on the biological fate of model colloidal drug carriers [J]. Biochim Biophys Acta, 2001,1514(2):261 -279.
[15] Bae KH, Ha YJ, Kim C, et al. Pluronic/chitosan shell cross-linked nanocapsules encapsulating magnetic nanoparticles[J]. J Biomater Sci Polym Ed, 2008;19(12):1571-1583.
[16] Moghimi SM, Pavey KD, Hunter AC. Real-time evidence of surface modification at polystyrene lattices by poloxamine 908 in the presence of serum: in vivo conversion of macrophage-prone nanoparticles to stealth entities by poloxamine 908 [J]. FEBS Lett, 2003, 547(1-3): 177-182.
[17] Moghimi SM, Hunter AC. Poloxamers and poloxamines in nanoparticle engineering and experimental medicine [J]. Trends Biotechnol, 2000, 18(10):412-420.
[18] Sun W, Xie C, Wang H, et al. Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain [J]. Biomaterials, 2004, 25(15): 3065-3071.
[19] Kreuter J. Nanoparticulate systems for brain delivery of drugs [J]. Adv Drug Deliv Rev, 2001, 47(1):65-81.
[20] Peracchia MT, Fattal E, Desmaele D, et al. Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting [J]. J Control Release, 1999, 60(l):121-128.
[21] Fundaro A, Cavalli R, Bargoni A, et al. Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats [J]. Pharmacol Res, 2000,42(4):337-343.
[22] Gillies E R, Frechet J M J. Dendrimers and dendritic polymers in drug delivery[J]. Drug Discov Today, 2005, 10:35-43.
[23] Kojima C, Kono K, Maruyama K, et al. Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs[J]. Bioconjug Chem, 2000, 11(6): 910-917.
[24] Gurdag S, Khandre J, Stapels S, et al. Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and -resistant cell lines[J]. Bioconjug Chem, 2006,17:275-283.
[25] Singh Y, Palombo M, Sinko PJ. Recent trends in targeted anticancer prodrug and conjugate design[J]. Curr Med Chem, 2008; 15(18): 1802-26.
[26] Pridgen EM, Langer R, Farokhzad OC. Biodegradable, polymeric nanoparticle delivery systems for cancer therapy[J]. Nanomed, 2007;2(5):669-680.
[27] Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy[J]. Adv Drug Deliv Rev, 2004; 56(11):1649-1659.
[28] Minko T, Dharap SS, Pakunlu RI, et al. Molecular targeting of drug delivery systems to cancer[J]. Curr Drug Targets, 2004; 5(4):389-406.
[29] Thomas T P, Majoros I J, Kotlyar, et al. Targeting and inhibition of cell growth by an engineered dendritic nanodevice[J]. J Med Chem, 2005,48(11):3729-3735.
[30] Patui A K, Kukowska-Latallo J F, Baker JR J R, et al. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex[J]. Adv Drug Deliver Rev, 2005, 57:2203-2214.
[31] Majoros I J, Myc A, Thomas T, et al. PAMAM dendrimer-based multifunctional for cancer therapy: synthesis, characterization, and founctionality[J]. Biomacromolecules, 2006, 7(2) :572-579.
[32] Shukla S., Wu G., Chatterjee M, et al. Synthesis and biological evaluation of folate receptor targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy[J]. Bioconjug. Chem., 2003, (14): 158-167.
[33] Gong Wu, Rolf F. Barth, Weilian Yang, et al. Targeted delivery of methotrexate to epidermal growth factor-positive brain tumors by means of cetuximab(IMC-C225) dendrimer bioconjugates. Mol Cancer Ther. 2006,5(1):52-59.
[34] Li Y, Ogris M, Wagner E, et al. Nanoparticles bearing polyethyleneglycol-coupled transferrin as gene carriers:preparation and in vitro evaluation[J]. Int J Pharm, 2003, 259(1-2): 93-101.
[35] Leamon CP.Folate-targeted drug strategies for the treatment of cancer[J]. Curr Opin Investig Drugs, 2008; 9(12):1277-1286
[36] Yoshizawa T, Hattori Y, Hakoshima M, et al Folate-linked lipid-based nanoparticles for synthetic siRNA delivery in KB tumor xenografts[J]. Eur J Pharm Biopharm, 2008; 70(3): 718-725.
[37] Glickson JD, Lund-Katz S, Zhou R et al. Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents[J]. Adv Exp Med Biol,2009; 645:227-239.
[38] Williams, J.. The evolution of transferrin. Trends Biochem. Science. 1982,7(11):394-397.
[39] Chasteen ND. The identification of the probable locus of iron and anion binging in the transferrin. Trends Biochem. Scl. 1983, 8(8):272-275.
[40] Huebers HA, Finch CA. The physiology of transferrin and transferrin receptors[J]. Physiol Rev, 1987, 67: 52-58.
[41] Vyas SP, Sihorkar V. Endogenous carriers and ligands in non-immunogenic site-specific drug delivery[J]. Adv Drug Deliv Rev, 2000, 43(2-3): 101-164.
[42] Li H, Sun H, Qian ZM. The role of the transferrin-transferrin-receptor system in drug delivery and targeting. Trends Pharmacol Sci. 2002,23(5):206-209.
[43] Yeh C-JG, Faulk WP. Killing of human tumor cells in culture with adriamycin conjugates of human transferrin[J]. Clin Immunol Immunopathol.1984, 32: 1-11.
[44] Fritzer M, Szekeres T, Szuts V, Jarayam HN, et al. Cytotoxic effects of a doxorubibin-transferrin conjugate in multidrug-resistant KB cells[J].Biochem Pharmacol, 1996, 51: 489-493.
[45] Singh M, Atwal H, Micetich R. Transferrin directed delivery of adriamycin to human cells[J]. Anticancer Res, 1998, 18(3A): 1423-1427.
[46] Lai H, Sasaki T, Singh NP, et al. Effects of artemisinin-tagged holotransferrin on cancer cells[J]. Life Sci, 2005, 76: 1267-1279.
[47] Jiang YY, Liu C, Hong MH, et al. Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system: design,synthesis, and biological evaluation[J]. Bioconjug Chem, 2007,18(1): 41-49.
[48] Suzuki R, Takizawa T, Kuwata Y, et al. Effective antitumor activity of Oxaliplatin encapsulated in transferrin-PEG-liposome[J]. Int J Pharm, 2008,346(1-2): 143-150.
[49] Masunaga S, Kasaoka S, Maruyama K, et al The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-(10)B (GB-10) as (10)B-carriers for boron neutron capture therapy[J]. Int J Radiat Oncol Biol Phys, 2006, 66(5):1515-22.
[50] Anabousi S, Bakowsky U, Schneider M, et al. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer[J]. Eur J Pharm Sci, 2006,29: 367-374.
[51] Kobayashi T, Ishida T, Okada Y, et al. Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells[J]. Int J Pharm, 2007, 329(1-2): 94-102.
[52] Sahoo SK, Labhasetwar V. Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J]. Mol Pharm, 2005, 2(5):373-383.
[53] Hong MH, Zhu SJ, Jiang YY, Tang GT, Pei YY. Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin. Journal of Controlled Release. 2009,133:96-102.
[54] Qing-Yong Li, Yuan-Gang Zu, Rong-Zhen Shi, et al. Review Camptothecin: current perspectives. Current Medicinal Chemistry. 2006,13(17):2021 -2039.
[55] Joseph F Piaaolato, Leonard B Saltz. The camptothecin. Lancet. 2003,361:2235-2242.
[56] Masato Watanabe, Kumi Kawano, Kazunori Toma, et al. In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid human serum albumin. Journal of Controlled Release. 2008,127:231-238.
[57] Daoud SS, Fetouh MI, Giovaneua BC. Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts.Anti-cancer Drugs. 1995, 6(1):83-95.
[58] Kumi Kawwno, Masato Watanabe, Tatsuhiro Yamamoto. Et al. Enahced antitumor effect of camptothecin loaded in long-circulatin polymeric micelles. Journal of Controlled Release. 2006, 112:329-332.
[59] Shicheng Yang, Jiabi Zhu, Yu Lu, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharmaceutical Research.1999, 16(5):751-757.
[60] Ertl B, Platzer P, Wirth M, et al. Poly(D,L-lactic-co-glycolic acid) microspheres for sustained delivery and stabilization of camptothecin.Journal of controlled release. 1999, 61(3):305-317.
[61] Tong W. Wang L, D'Souza MJ. Evaluation of PLGA microspheres as delivery system for antitumor agent camptothecin. Drug Dev Ind Pharm.2003, 29(7):745-756.
[62] Thomas Schluep, Jianjun Cheng, Kay T. Khim et al. Pharmacokenetics and biodistribution of the camptothecin-polymic conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemotheapy Pharmcology. 2006, 57:654-662.
[63] Anita Lalloo, Piyun Chao, Peidi Hu, et al. Pharmacokinetic and pharmcodynamic evaluation of a novel in situ forming poly(ethylene glycol)-based hydrogel for the controlled delivery of the camptothecin.Journal of Controlled Release. 2006, 112:333-342.
[1]Qing-Yong Li,Yuan-Gang Zu,Rong-Zhen Shi,et al.Review Camptothecin:current perspectives.Current Medicinal Chemistry[J].2006,13(17):2021-2039.
[2]Olivier Lavergne,Laurence Lesueur-Ginot,Francesc Pla Rodas,et al.Homocamptothecin:syntheisi and antitumor activity of novel E-ring-modifed camptothecin analogues.Journal of medicinal chemistry[J].1998,41:5410-5419.
[3]C.Kojima,K.Kono,K.Maruyama,et al.Synthesis of Polyamidoamine Dendrimers having Poly(ethyleneglycol) grafts and their ability to encapsulate anticancer drugs[J].Bioconjugate chemistry,2000,11:910-917.
[4]GF,Pan,Y.Lemmouchi,E.O.Akala,et al.Studies on PEGylated and drug-loaded PAMAM Dendrimers[J].Journal of Bioactive and Compatible Polymers.2005,20:113-128.
[5]Dan Luo,Kraig,Haverstick,Nadya Belcheva,Ernest Han,W.Mark Saltzman.Poly(ethylene glycol)-conjugated PAMAM Dendrimer for biocompatible,high-efficiency DNA delivery[J].Macromolecules,2002,35:3456-3462.
[6]D.Bhadra,S.Bhadra,S.Jain,N.K.Jain.A PEGylated dendritic nanoparticulate carrier of fluorouacil[J].International Journal of Pharmaceutics,2003,257:111-124.
[7]Rong-Qin Huang,Ying-Hua Qu,Wei-Lun Ke,Jian-Hua Zhu,Yuan-Ying Pei,Chen Jiang.Efficient gene delivery targeted to the brain using a transferring-conjugated polyethyleneglycol-modified polyamidoamine dendrimer[J].The FASEB Journal,2007,21:1117-1125.
[8]Michelle K Calabretta,Amit Kumar,Alison M.McDermott,Chengzhi Cai.Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups[J].Biomacromolecules,2007,(8):1807-1811.
[9]Samaresh Ghosh.Novel poly(ethylene glycol) embedded polyamidoamine side chain dendritic polyurethane architecture: synthesis and preliminary studies on the cytotoxicity and interaction with tryptophan molecule[J].Biomacromolecules. 2004. 5:1602-1605.
[10] Chie Kljima, Yoko Toi, Atsushi Harada, Kenji Kono. Preparation of poly(ethylene glycol) -attached dendrimers encapsulating photosensitizers for application to photodynamic therapy[J]. Bioconjugate chem.2007.18:663-670.
[11] Michelle K,Calabretta, Amit Kumar, Alison M. McDermott, Chengzhi CAI.Antibacterial activities of poly(amidoamine ) dendrimers terminated with amino and poly(ethylent glycol groups[J]. Biomacromolecules. 2007, 8:1807-1811.
[12] Tatsuya Okuda, Shigeru Kawakami, Tadahiro Maeie, Takuro Niidome,Fumiyoshi Yamashita, Mitsuru Hashida. Biodistubution characetristics of amino acid dendrimers and their PEGylated derivatives after intravenous dministration[J]. Journal of Controlled Release. 2006. 114:69-77.
[13] Gaur U, Sahoo SK, De TK, et al. Biodistribution of fluoresceinated dextran using novel nanoparticles evading reticuloendothelial system[J]. Int J Pharm,2000,202(1-2): 1-10.
[14] Duncan R, Connors TA, Meada H. Drug targeting in cancer therapy: the magic bullet, what next? [J] J Drug Target, 1996, 3(5): 317-319.
[15] Hua Lu, Haixia Lin, Yi Jiang, Xinguang Zhou, Beili Wu, et al. Synthesis and antitumor activity of 20-o-linked succinate-based camptothecin ester derivatives[J]. Letters in Drug Design & Discovery, 2006 ,3(2) :83-86.
[16] Tamar Minko, Pankaj V. Paranjpe, Bo Qiu, Anita Lalloo, Roney Won, Stanley Stein, Patrick J. Sinko. Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethyleneglycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cell[J]. Cancer Chemother Pharmacol, 2002, 50:143-150.
[17] Deshan Yu, Ping Peng, Sonia S. Dharap, Yang Wang, Mary Mehlig, Pooja Chandna, Hong Zhao, David Filpula, Karen Yang, Vima Borowski, Gerrit Borchard, Zhihua Zhang, Tamara Minko. Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo[J]. Journal of Controlled Release, 2005, 110:90-102.
[18]Pandaj V.Paranjpe,Yu Chen,Vladyslav Kholodovych,Willian Welsh,Stanley Stein,Patrick J.Sinko.Tumor-targeted bioconjugate based delivery of camptothecin:design,synthesis and in vitro evaluation[J].Journal of Controlled Release,2004,100:275-292.
[19]Jack W.Singer,Rama Bhatt,John Tulinkdy,Kent R.Buhler,Eveline Heasley,Peter Klein,Peter de Vris.Water-soluble poly-(L-glutamic acid)-Gly-camptothecin conjugates enhance camptothecin stability and efficacy in vivo[J].Journal of Controlled Release,2001,74:243-247.
[20]Thomas Schluep,Jianjun cheng,Kay T.Khin,Mark E.Davis.Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice[J]Cancer Chemother Pharmacol,2006,57:654-662.
[21]V.R.Caiolfa,M.Zamai,A.Fiorino,E.Frigerio,C.Pellizzoni,R.d'Argy,A.Ghiglieri,M.G.Castelli,M.Farao,E.Pesenti,M.Gigli,F.Angelucci,A.Suarato.Polymer-bound camptothecin:initial biodistribution and antiumor activity studies[J].Journal of Controlled Release,2000,65:105-119.
[22]Cheol Moon,Young Min Kwon,Won Kyu Lee,Yoon Jeong Park,Li Chien Chang,Victor C.Yang.A novel polyrotaxane-based intracellular delivery system for camptothecin:in vitro feasibility evaluation[J].Journal of Biomedical Materials Research Part A 2008,84(1):238-246.
[23]Yeh C-JG,Faulk WP.Killing of human tumor cells in culture with adriamycin conjugates of human transferrin[J].Clin Immunol Immunopathol.1984,32:1-11.
[24]Lai H,Sasaki T,Singh NP,et al.Effects of artemisinin-tagged holotransferrin on cancer cells[J].Life Sci,2005,76:1267-1279.
[25]Suzuki R,Takizawa T,Kuwata Y,et al.Effective antitumor activity of Oxaliplatin encapsulated in transferrin-PEG-liposome[J].Int J Pharm,2008,346(1-2):143-150.
[26]Kobayashi T,Ishida T,Okada Y,et al.Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells[J].Int J Pharm,2007,329(1-2):94-102.
[27]Sahoo SK,Labhasetwar V.Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J].Mol Pharm,2005,2(5):373-383.
[28]Abela RA,Qian J,Xu L,et al.Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells[J].Cancer Gene Ther,2008,15(8):496-507.
[29]Jiang YY,Liu C,Hong MH,et al.Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system:design,synthesis,and biological evaluation[J].Bioconjug Chem,2007,18(1):41-49.
[30]Hong MH,Zhu SJ,Jiang YY,Tang GT,Pei YY.Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin[J].Journal of Controlled Release.2009,133:96-102
[31]Mao H,Roy K,Troung-Le VL,et al.Chitosan-DNA nanoparticles as gene carriers:synthesis,characterization and transfection efficiency[J],J Control Release,2001,70:399-421.
[32]Citoles L,Ferreras M,Munoz R,et al.Targeting cancer cells with transferrin conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrinb or ebulin l[J].Cancer Letters,2002,184:29-35.
[33]Kursa M,Walker GF,Roessler V,et al.Novel shielded tranferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer[J].Bioconjugate Chem,2003,14:222-231.
[34]Wagner E,Zenke M,Cotton M,et al.Transferrin-polycation conjugates ascarriers for DNA uptake into cells[J].Biochemistry,1990,87(5):3410-3414.-27]
[35]Duncan R.J.S,Weston P.D,Wrigglesworth R.A new reagent which may be used to introduce sulfhydryl groups into proteins,and its use in the preparation of conjugates for immunoassay[J].Analytical Biochemistry,1983,132:68-73.
[36]Kratz F,Beyer U,Schumacher P,et al.Synthesis of new maleimide derivatives of daunorubicin and biological activity of acid labile transferrin conjugates[J].Bioorganic & Medicinal Chemistry Letters,1997,7(5):617-622.
[37]Ellman G.L.Tissue sulfhydryl groups[J].Archives of Biochemistry and Biophysics,1959,82:70-77.
[38]Antonio Quintana,Ewa Raczka,Lars Piehler,Inhan Lee,Andrzej Myc,Istvan Majoros,Anil K.Patri,Thommey Thomas,James Mule,James R.Baker,Jr.Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor[J]. Pharmceutical Research, 2002,19(9): 1310-1316.
[39] Youngseon Choi, Thommey Thomas, Alina Kotlyar, James R. Baker, Jr.Synthesis and functional evaluation of DNA-assembled Polyamidoamine Dendrimer clusters for cancer cell-specific targeting[J]. Chemistry and Biology, 2005,12:35-43.
[40] Mohamed, EI-Sayed, Mohammad F. Kiani, Mike D. Naimark, Ahmed H.Hikal, Hamidreza Ghandehari. Extravasation of Poly(amidoamine) (PAMAM) Dendrimers across microvascular network endothelium[J].Pharmaceutical Research, 18(1):23-28.
[41] Tsutomu Yasukawa, Hideya Kimura, Yasubiko Tabata, Hideki Miyamoto,Yosbibito Honda, Yosbito Ikada, Yuibciro Ogura. Targeted delivery of anti-angiogenic agent TNP-470 using water-soluble polymer in the treatment of choroidal neovascularization[J]. Investigative Ophthalmology & Visual Science, 1999, 40(11): 2690-2696.
[42] Heman Sarin, Ariel S Kanevsdy, Haitao Wu, Kyle R Brimacombe, Steve H Fung, Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells[J]. Journal of Translational Medicine. 2008. 6:80
[1]Jiang YY,Liu C,Hong MH,et al.Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system:design,synthesis,and biological evaluation[J].Bioconjug Chem,2007,18(1):41-49
[2]Fritzer M,Barabas K,Sz(u|¨)ts V,et al.Cytotoxicity of a transferring-adriamycin conjugate to anthracycline-resistant cells[J].Int.J.Cancer,1992,52:619-623.
[3]Berczi A,Barabas K,Sizensky J.A.,et al.Adriamycin conjugates of human transferring bind transferring receptors and kill K562 and HL60 cells[J].Archives of Biochemistry and Biophysics,1993,300(1):356-363.
[4]D'Alessandro A.M.,D'Andrea G,Ciccio L.D.,et al.3'-Azido-3'-deoxythymidine reduces the rate of transferring receptorendocytosis in K562 cells[J].Biochimica et Biophsica Acta,1999,1450:232-241.
[5]Perez G,Garbossa G,Sassetti B,et al.Interference of aluminium on iron metabolism in erythroleukaemia K562 cells[J].Journal of InorganicBiochemistry,1999.76:105-112.
[6]Kircheis R,Blessing T,Brunner S,et al.Tumor targeting with surface-shielded ligand-polycation DNA complexes[J].Journal of Controlled release,2001,72:165-170.
[7]Fritzer M,Szekeres T,Sz(u|¨)ts V,et al.Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells[J].Biochemical Phamacology,1996,51:489-493.
[8]Tanaka T,Kaneo Y,Miyashita M.Synthesis of transferring-mitomycin C conjugate as a receptor-mediated drug targeting system[J].Bio Pharm Bull,1995,19(5):774-777.
[9]Maruyama K,Ishida O,Kasaoka S,et al.Intracellular targeting of sodium mercaptoundecahydrododecaborate(BSH) to solid tumors by transferring-PE liposomes,for boron nertron-capture therapy(BNCT)[J].Journal of Controlled release.2004,98:195-207.
[10]Voinea M,Dragomir E,Manduteanu I,et al.Binding and uptake of transferring-bound liposomes targeted to transferring receptors of endothelial cells[J].Vascular Pharmacology,2002,39:13-20.
[11]Citores L,Ferreras M,Munoz R,et al.Targeting cancer cells with transferring conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrinb or ebulin l[J].Cancer Letters,2002,184:29-35.
[12]Tanaka T,Miyashita SM,Kaneo YF.Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].International Journal of Pharmaceutics,2004,277:39-61.
[13]林溪,黄秀旺.人转铁蛋白-阿霉素结合物的制备及其体外细胞毒作用[J].肿瘤,2000,20(4):263-265.
[14]林溪,黄秀旺,柯丹如等.人转铁蛋白-甲氨喋呤结合物对人肝细胞、人肝癌细胞体外细胞毒的作用特点[J].福建医科大学学报,2001,35(1):7-9.
[15]Sahoo SK,Labhasetwar V.Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J].Mol Pharm,2005,2(5):373-383.
[16]Sorensen M,Sehested M,Jensen PB.Effect of cellular ATP depletion on topoisomerase Ⅱ poisons.Abrogation Of cleavable-complex formation by etoposide but not by amsacrine[J].Mol Pharmacol,1999,55(3):424-431.
[17]Mousavi SA,Malerod L,Berg T,et al.Clathrin-dependent endocytosis[J].Biochem J,2004,377:1-16.
[18]Fielding CJ,Fielding PE.Caveolae and intracellular trafficking of cholesterol [J].Adv Drug Deliv Rev,2001,49(3):251-264.
[19]Sieczkarski SB.Whittaker GR.Dissecting virus entry via endocytosis[J].J Gen Virol,2002,83:1535-1545.
[20]Gruenberg J.The endocytic pathway:a mosaic of domains[J].Nat Rev,Mol Cell Biol,2001,2(10):721-730.
[21]Casey CA,Wiegert RL,Tuma DJ.Effect of hyperosmolarity on both receptor-mediated and fluid-phase endocytosis in ethanol-fed animals[J].Biochem Pharmacol,1995,49:1117-1123.
[22]Chen J,Li G,Lu J,et al.A novel type of PTD,common helix-loop-helix motif,could efficiently mediate protein transduction into mammalian cells[J].Biochem Biophys Res Commun,2006,347:931-940.
[23]Schnitzer JE,Oh P,Pinney E,et al.Filipin-sensitive caveolar-mediated transport in endothelium:Reduced transcytosis,scavenger endocytosis,and capillary permeability of selected macromolecules[J].J Cell Biol,1994,127:1217-1232.
[24]Kheirolomoom A,Ferrara KW.Cholesterol transport from liposomal delivery vehicles[J].Biomaterials,2007,28:4311-4320.
[25]Kitchens KM,Kolhatkar RB,Swaan PW,et al.Endocytosis inhibitors prevent poly(amidoamine) dendrimer internalization and permeability across Caco-2cells[J].Mol Pharm,2008,5:364-369.
[26]Jevprasesphant R,Penny J,Attwood D,et al.Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity[J].Pharm Res,2003,20:1543-1550.
[27]Jiang S,Rhee SW,Gleeson PA,et al.Capacity of the Golgi Apparatus for Cargo Transport Prior to Complete Assembly[J].Mol Biol Cell,2006,17(9):4105-4117.
[28]Ruth Duncan,Lorella Izzo.Dendrimer biocompatibility and toxicity[J].Advanced drug delivey reviews.2005.57:2215-2237.
[29]Hui-ting Chen,Michael F.Neerman,Alan R.Parrish et al.Cytotoxicity, hemolysis,and acute in vivo toxicity fo dendrimers based on melamine,candidate vehicles for drug delivery[J].J.AM.CHEM.SOC.2004.126(32):10044-10048.
[30]aniels TR,Delgado T,Helguera G,et al.The transferrin receptor part Ⅱ:targeted delivery of therapeutic agents into cancer cells[J].Clin Immunol,2006,121:159-176.
[31]Li H,Sun H,Qian ZM.The role of the transferrin-transferrin-receptor system in drug delivery and targeting[J].Trends Pharmacol Sci,2002,23(5):206-209.
[32]Anabousi S,Bakowsky U,Schneider M,et al.In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer[J].Eur J Pharm Sci,2006,29:367-374.
[33]Xiangyang Wang,Xiang Zhou,Sidney M.Hecht.Role of the 20-hydroxyl group in camptothecin binding by the Topoisomerase 1-DNA binary complex[J].Biochemistry,1999,38:4374-4381.
[34]Beverly A.Teicher.Next generation topoisomerase 1 inhibitors rationale and biomarker strategies[J].Biochemical Pharmcology,2008,75:1262-1271.
[35]Andrew J.Hudson,Nadia Normand,John Ackroyd.Cellular delivery of hammerhead ribozymes conjugated to a transferrin receptor antibody[J].International Journal of Pharmaceutics.1999,182:49-58.
[36]Gabor F,Schwarzbauer A,Wirth M.Lectin-mediated drug delivery:binding and uptake of BSA-WGA conjugates using the Caco-2 model[J].Int J Pharm,2002,237(1-2):227-239.
[37]Hongyan Li,Zhongmimg Qian.Transferrin/transferring receptor-mediated drug delivery[J].Medicinal Research Reviews.2002,22(3):225-250.
[38]Ping-Shan Lai,P.-J.L.,Cheng-Liang Peng,Chin-Ling Pai,Wei-Nen Yen,Ming-Yi Huang,Tai-Horng Young,Ming-Jium Shieh.Doxorubin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy[J].Journal of Controlled Release 2007,(122):39-46.
[1] Thomas Schluep, Jianjun Cheng, Kay T. Khim et al. Pharmacokenetics and biodistribution of the camptothecin-polymet conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemotheapy Pharmcology. 2006, 57:654-662.
[2] Anita Lalloo, Piyun Chao, Peidi Hu, et al. Pharmacokinetic and pharmcodynamic evaluation of a novel in situ forming poly(ethylene glycol)-based hydrogel for the controlled delivery of the camptothecin. Journal of Controlled Release. 2006,112:333-342.
[3] Dennis O. Scott, Dilbir S. Bindra, Valentino J. Stella. Plasma pharmacokinetics of the lactone and carboxylate forms of 20(S)-camptothecin in anesthetized rats.Pharmaceutical Research. 1993, 10(10):1451-1457.
[4] Kumi Kawwno, Masato Watanabe, Tatsuhiro Yamamoto. Et al. Enahced antitumor effect of camptothecin loaded in long-circulatin polymeric micelles.Journal of Controlled Release. 2006, 112:329-332.
[5] Shicheng Yang, Jiabi Zhu, Yu Lu, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharmaceutical Research. 1999,16(5):751-757.
[6] Tsutsumi Y, Kihira T, Tsunoda S, et al. Molecular design of hybrid tumor necrosis factor-αⅢ: polyethylene glycol-modified tumor necrosis factor-a has markedly enhanced antitumor potency due to long plasma half-life and higher tumor accumulate on. J Pharmacol Exp Ther. 1996,278:1006-1011.
[7] Imoto H, Sakamura Y, Ohkouchi K, et al. Disposition characteristics of macromoleules in the perfused tissue-isolated tumor preparation. Cancer Research. 1992, 52:4396-4401.
[8] Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting [J].Adv Enzyme Regul, 2001,41(1):189-207.
[9] Maeda H, Wu J, Sawa T, et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review [J]. J Control Release, 2000, 65(1-2):271-284.
[10] Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS [J]. J Control Release,2001,74(1-3):47-61.
[11] Tanaka T, Shiramoto S, Miyashita M, et al. Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].Int J Pharm,2004,277(1-2):39-61.
[12]Greenwald RB.PEG drugs:an overview[J].J Control Release,2001,74(1-3):159-171.
[13]Shicheng Yang,Lifang Lu,Ying Cai,ea tl.Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.Journal of Controlled Release.1999,59:299-307
[14]Jultani A,Li C,Ozen M,et al.Paclitaxel and water-soluble poly(L-glutamic acid)- paclitaxel,induce direct chromosomal abnormalities and cell death in a murine metastatic melanoma cell line[J].Anticancer Res,1997,17:4269-4274.
[15]Zunino F,Giuliani F,Savi G,et al.Anti-tumor activity of Daunorubicin linked to poly-L-aspartic acid[J].Int J Cancer,1982,30:465-470.
[16]Greenwald RB,Choe YH,McGuire J,et al.Effective drug delivery by PEGylated drug conjugates[J].Adv Drug Deliv Rev,2003,55(2):217-250.
[17]Hong MH,Zhu SJ,Jiang YY,Tang GT,Pei YY.Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin.Journal of Controlled Release.2009,133:96-102
[18]XueMing Li,LiYan Ding,Yuanlong.Xu,et al.Targeted delivery of doxorubicin using stealth liposomes modified with transferrin.International Journal of Pharmaceutics.2009,373:116-126.
[19]Yu Gao,Lingli Chen,Wangwen Gu,et al.Targeted nanoassembly loaded with Docetaxel improves intracellular drug delivery and efficacy in murine breast cancer model.Molecular Pharmaceutics.2008,5:1044-1054.
[20]Masato Watanabe,Kumi Kawano,Kazunori Toma,et al.In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid human serum albumin.Journal of Controlled Release.2008,127:231-238.
[1]Namita S,Peter A.Ki67 structure,function and new antibodies[J]J Pathol,1992,168:161
[2]Marie C.Prewett,Andrea T.Hooper,Rajiv Bassi,et al.Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irrnotecan(CPT-11) against human colorectal tumor xenografts.Clinical Cancer Research.2002,8:994-1003.
[3]Ying Chau,Robert Padera,Natalie M.Dang,et al.Antitumor efficacy of a novel polymer-peptide-drug conjugate in human tumor xenograft models.Internation Journal of Cancer.2006,118:1519-1526.
[1]ESFAND R,TOMALIA DA.Poly(amidoamine)(PAMAM) dendrimers:from biomimicry to drug delivery and biomedical applications.Drug Discov Today,2001,6(8):427-436.
[2]GILLIES E R,FRECHET J M J.Dendrimers and dendritic polymers in drug delivery[J].Drug Discov Today,2005,10:35-43.
[3]ROBERTS J C,BHALGAT M K,ZERA R T.Preliminary biological evaluation of polyamidomine(PAMAM) Starbutst~(TM) dendrimers[J].J Biomed Mater Res,1996,30:53-65.
[4]JEVPRASESPHANT R,PENNY J,JALAL R,el al.The influence of surface modification on the cytotoxicity of PAMAM dendrimers[J].Int J Pharm,2003,(252):263-266.
[5]DOMANSKI D M,KLAJNERT B,BRYSZEWSKA M.Influence of PAMAM dendrimers on human red blood cells[J].Bioelectrochemistry,2004,63:189-191.
[6]EL-SAYED M,RHODS C A,G1NSKE M,et al.Transport mechanism of polyamidoamine dendrimers across Caco-2 cell monolayers[J],Int J Pharm,2003,(265):151-157.
[7]KOJIMA C,KONO K,MARUYAMA K,et al.Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs[J].Bioconjug Chem,2000,11(6):910-917.
[8]GURDAG S,KHANDARE J,STAPELS S,et al.Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and -resistant cell lines[J].Bioconjug Chem,2006,17:275-283.
[9]BHADRA D,BHADRA S,JAIN S,et al.A PEGylated dendritic anoparticulate carrier of fluorouracil[J].Int J Pharm,2003,(257):111-124.
[10]PAN G F LEMMOUCHI Y,EMMANUEL O,et al.Studies on PEGylated and drug-loaded PAMAM dendrimers[J].J Bioact Compat Pol,2005,20:113-128.
[11]KONDA S D,AREF M,WANG S,et al.Specific targeting of folate-dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts[J].Magnetic Resonance Materials in Physics,Biology and Medicine 2001,12:104-113.
[12]QUINTANA A,RACZKA E,PIEHLER L,et al.Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor[J].Pharm Res,2002,19(9):1310-1316.
[13]MAJOROS I J,THOMAS T P,MEHTA C B,et al.Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy[J].J Med Chem 2005,48(19):5892-5899
[14] THOMAS T P, MAJOROS I J, KOTLYAR A, et al. Targeting and inhibition of cell growth by an engineered dendritic nanodevice[J]. J Med Chem, 2005,48(11):3729-3735.
[15] PATUI A K, KUKOWSKA-LATALLO J F, BAKER JR J R, et al. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex[J]. Adv Drug Deliver Rev, 2005, 57:2203-2214.
[16] MAJOROS I J, MYC A, THOMAS T, et al. PAMAM dendrimer-based multifunctional for cancer therapy: synthesis, characterization, and founctionality[J]. Biomacromolecules, 2006,7(2) :572-579.
[17] SHUKLA S., WU G., CHATTERJEE M, et al. Synthesis and biological evaluation of folate receptor targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy[J]. Bioconjug. Chem., 2003, (14): 158-167.
[18] YANG W, BARTH F, WU G, et al. Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas[J]. Appl Radiat Isotopes, 2004,(61): 981-985.
[19] YANG H, LOPINA S T. In vitro enzymatic stability of dendritic peptides[J/OL]. J Biomed Mater Res, 2006, 76A(2), 398-407[2005-11-03]. http://www.iterscienct.wiley.com
[20] SAMHAROV D V, JIE A F, FILIPPOV D V, et al. Binding and retention of polycationic peptides and dendrimers in the vascular wall[J]. FEBS Lett. 2003, 537:6-10.
[21] SHUKLA R, THOMAS T P, PETERS J, et al. Tumor angiogenic vasculature targeting with PAMAM dendrimer-RGD conjugates[J]. Chem. Commun, 2005, 5739-5741.
[22] EICHMAN J D, BIELINSKA A U, KUKOWSKA-LATALLO J F, et al. The use of PAMAM dendrimers in the efficient transfer of genetic material into cells[J]. Pharmaceutical SCI &Technol Today, 2000, (3)7:232-245.
[23] BIELINSKA AU, CHEN C L, JOHNSON J, et al. DNA complexing with polyamidoamine dendrimers: implications for transfection[J]. Bioconjug Chem, 1999, 10:843-850.
[24]LUO D, HAVERSTICK K, BELCHEVA N, et al. Poly(ethylene glycol)-conjugated PAMAM dendrimer for biocompatible, high-efficiency DNA delivery[J]. Macromolecules,2002,35(9):3456-3462.
[25] MARUYAMA-TABATA H, HARADA Y, MATSUMURA T, et al. Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer[J].Gene Ther, 2000, 7(1):53-60.
[26] HOWARD DS, RIZZIERRI DA, GIMES B, et al. Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer[J]. Leukemia. 1999, 13(10): 1608-1616.
[27] HUDDE T, RAYNER SA, COMER RM, et al. Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium[J]. Gene Therapy, 1999,6:939-943.
[28] HUANG R Q, YANG W L, JIANG C, et al. Gene delivery into brain capillary endothelial cells using Antp-modified DNA-loaded nanoparticles[J]. Chem Pharm Bull 2006,54(9):1254-1258.
[29] HYUNMIN K, ROBERT DL, MICHAEL H F, et al. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides[J]. Pharm Res, 2005,22(12):201-2106.
[30] KIM J B, CHOI J S, NAM K, et al. Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg[J]. J Control Release, 2006,114:110-117.
[2]Maeda H.The enhanced permeability and retention(EPR) effect in tumor vasculature:the key role of tumor-selective macromolecular drug targeting [J].Adv Enzyme Regul,2001,41(1):189-207.
[3]Maeda H,Wu J,Sawa T,et al.Tumor vascular permeability and the EPR effect in macromolecular therapeutics:a review[J].J Control Release,2000,65(1-2):271-284.
[4]Maeda H,Sawa T,Konno T.Mechanism of tumor-targeted delivery of macromolecular drugs,including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS[J].J Control Release,2001,74(1-3):47-61.
[5]Tanaka T,Shiramoto S,Miyashita M,et al.Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].Int J Pharm,2004,277(1-2):39-61.
[6]Greenwald RB.PEG drugs:an overview[J].J Control Release,2001,74(1-3):159-171.
[7]van Vlerken LE,Vyas TK,Amiji MM.Poly(ethylene glycol)-modified Nanocarriers for Tumor-targeted and Intracellular Delivery[J].Pharma Res,2007,24(8):1405-1414.
[8]Stolnik S,Illum L,Davis SS.Long circulating microparticulate drug carriers [J].Adv Drug Deliv Rev,1995,16(2-3):195-214.
[9]Redhead HM,Davis SS,Illum L.Drug delivery in poly(lactide-co-glycolide)nanoparticles surface modified with poloxamer 407 and poloxamine 908:in vitro characterisation and in vivo evaluation[J].J Control Release,2001,70(3):353-363.
[10]Zhang Y,Kohler N,Zhang M.Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake[J].Biomaterials,2002,23(7):1553-1561.
[11]Gref R,L(u|¨)ck M,Quellec P,et al.'Stealth' corona-core nanoparticles surface modified by polyethylene glycol(PEG):influences of the corona(PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption[J].Colloids Surf B Biointerfaces,2000,18(3-4):301-313.
[12] Sheng Y, Liu C, Yuan Y,et al. Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan[J].Biomaterials, 2009, 30(12):2340-2348.
[13] Li YP, Zhou ZH, Pei YY, et al. PEGylated polycyanoacrylate nanoparticles as salvicine carriers: synthesis, preparation, and in vitro characterization [J].Acta Pharmacol Sin, 2001, 22(7):645-650.
[14] Stolnik S, Daudali B, Arien A, et al. The effect of surface coverage and conformation of poly (ethylene oxide) (PEO) chains of poloxamer 407 on the biological fate of model colloidal drug carriers [J]. Biochim Biophys Acta, 2001,1514(2):261 -279.
[15] Bae KH, Ha YJ, Kim C, et al. Pluronic/chitosan shell cross-linked nanocapsules encapsulating magnetic nanoparticles[J]. J Biomater Sci Polym Ed, 2008;19(12):1571-1583.
[16] Moghimi SM, Pavey KD, Hunter AC. Real-time evidence of surface modification at polystyrene lattices by poloxamine 908 in the presence of serum: in vivo conversion of macrophage-prone nanoparticles to stealth entities by poloxamine 908 [J]. FEBS Lett, 2003, 547(1-3): 177-182.
[17] Moghimi SM, Hunter AC. Poloxamers and poloxamines in nanoparticle engineering and experimental medicine [J]. Trends Biotechnol, 2000, 18(10):412-420.
[18] Sun W, Xie C, Wang H, et al. Specific role of polysorbate 80 coating on the targeting of nanoparticles to the brain [J]. Biomaterials, 2004, 25(15): 3065-3071.
[19] Kreuter J. Nanoparticulate systems for brain delivery of drugs [J]. Adv Drug Deliv Rev, 2001, 47(1):65-81.
[20] Peracchia MT, Fattal E, Desmaele D, et al. Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting [J]. J Control Release, 1999, 60(l):121-128.
[21] Fundaro A, Cavalli R, Bargoni A, et al. Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats [J]. Pharmacol Res, 2000,42(4):337-343.
[22] Gillies E R, Frechet J M J. Dendrimers and dendritic polymers in drug delivery[J]. Drug Discov Today, 2005, 10:35-43.
[23] Kojima C, Kono K, Maruyama K, et al. Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs[J]. Bioconjug Chem, 2000, 11(6): 910-917.
[24] Gurdag S, Khandre J, Stapels S, et al. Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and -resistant cell lines[J]. Bioconjug Chem, 2006,17:275-283.
[25] Singh Y, Palombo M, Sinko PJ. Recent trends in targeted anticancer prodrug and conjugate design[J]. Curr Med Chem, 2008; 15(18): 1802-26.
[26] Pridgen EM, Langer R, Farokhzad OC. Biodegradable, polymeric nanoparticle delivery systems for cancer therapy[J]. Nanomed, 2007;2(5):669-680.
[27] Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy[J]. Adv Drug Deliv Rev, 2004; 56(11):1649-1659.
[28] Minko T, Dharap SS, Pakunlu RI, et al. Molecular targeting of drug delivery systems to cancer[J]. Curr Drug Targets, 2004; 5(4):389-406.
[29] Thomas T P, Majoros I J, Kotlyar, et al. Targeting and inhibition of cell growth by an engineered dendritic nanodevice[J]. J Med Chem, 2005,48(11):3729-3735.
[30] Patui A K, Kukowska-Latallo J F, Baker JR J R, et al. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex[J]. Adv Drug Deliver Rev, 2005, 57:2203-2214.
[31] Majoros I J, Myc A, Thomas T, et al. PAMAM dendrimer-based multifunctional for cancer therapy: synthesis, characterization, and founctionality[J]. Biomacromolecules, 2006, 7(2) :572-579.
[32] Shukla S., Wu G., Chatterjee M, et al. Synthesis and biological evaluation of folate receptor targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy[J]. Bioconjug. Chem., 2003, (14): 158-167.
[33] Gong Wu, Rolf F. Barth, Weilian Yang, et al. Targeted delivery of methotrexate to epidermal growth factor-positive brain tumors by means of cetuximab(IMC-C225) dendrimer bioconjugates. Mol Cancer Ther. 2006,5(1):52-59.
[34] Li Y, Ogris M, Wagner E, et al. Nanoparticles bearing polyethyleneglycol-coupled transferrin as gene carriers:preparation and in vitro evaluation[J]. Int J Pharm, 2003, 259(1-2): 93-101.
[35] Leamon CP.Folate-targeted drug strategies for the treatment of cancer[J]. Curr Opin Investig Drugs, 2008; 9(12):1277-1286
[36] Yoshizawa T, Hattori Y, Hakoshima M, et al Folate-linked lipid-based nanoparticles for synthetic siRNA delivery in KB tumor xenografts[J]. Eur J Pharm Biopharm, 2008; 70(3): 718-725.
[37] Glickson JD, Lund-Katz S, Zhou R et al. Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents[J]. Adv Exp Med Biol,2009; 645:227-239.
[38] Williams, J.. The evolution of transferrin. Trends Biochem. Science. 1982,7(11):394-397.
[39] Chasteen ND. The identification of the probable locus of iron and anion binging in the transferrin. Trends Biochem. Scl. 1983, 8(8):272-275.
[40] Huebers HA, Finch CA. The physiology of transferrin and transferrin receptors[J]. Physiol Rev, 1987, 67: 52-58.
[41] Vyas SP, Sihorkar V. Endogenous carriers and ligands in non-immunogenic site-specific drug delivery[J]. Adv Drug Deliv Rev, 2000, 43(2-3): 101-164.
[42] Li H, Sun H, Qian ZM. The role of the transferrin-transferrin-receptor system in drug delivery and targeting. Trends Pharmacol Sci. 2002,23(5):206-209.
[43] Yeh C-JG, Faulk WP. Killing of human tumor cells in culture with adriamycin conjugates of human transferrin[J]. Clin Immunol Immunopathol.1984, 32: 1-11.
[44] Fritzer M, Szekeres T, Szuts V, Jarayam HN, et al. Cytotoxic effects of a doxorubibin-transferrin conjugate in multidrug-resistant KB cells[J].Biochem Pharmacol, 1996, 51: 489-493.
[45] Singh M, Atwal H, Micetich R. Transferrin directed delivery of adriamycin to human cells[J]. Anticancer Res, 1998, 18(3A): 1423-1427.
[46] Lai H, Sasaki T, Singh NP, et al. Effects of artemisinin-tagged holotransferrin on cancer cells[J]. Life Sci, 2005, 76: 1267-1279.
[47] Jiang YY, Liu C, Hong MH, et al. Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system: design,synthesis, and biological evaluation[J]. Bioconjug Chem, 2007,18(1): 41-49.
[48] Suzuki R, Takizawa T, Kuwata Y, et al. Effective antitumor activity of Oxaliplatin encapsulated in transferrin-PEG-liposome[J]. Int J Pharm, 2008,346(1-2): 143-150.
[49] Masunaga S, Kasaoka S, Maruyama K, et al The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-(10)B (GB-10) as (10)B-carriers for boron neutron capture therapy[J]. Int J Radiat Oncol Biol Phys, 2006, 66(5):1515-22.
[50] Anabousi S, Bakowsky U, Schneider M, et al. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer[J]. Eur J Pharm Sci, 2006,29: 367-374.
[51] Kobayashi T, Ishida T, Okada Y, et al. Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells[J]. Int J Pharm, 2007, 329(1-2): 94-102.
[52] Sahoo SK, Labhasetwar V. Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J]. Mol Pharm, 2005, 2(5):373-383.
[53] Hong MH, Zhu SJ, Jiang YY, Tang GT, Pei YY. Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin. Journal of Controlled Release. 2009,133:96-102.
[54] Qing-Yong Li, Yuan-Gang Zu, Rong-Zhen Shi, et al. Review Camptothecin: current perspectives. Current Medicinal Chemistry. 2006,13(17):2021 -2039.
[55] Joseph F Piaaolato, Leonard B Saltz. The camptothecin. Lancet. 2003,361:2235-2242.
[56] Masato Watanabe, Kumi Kawano, Kazunori Toma, et al. In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid human serum albumin. Journal of Controlled Release. 2008,127:231-238.
[57] Daoud SS, Fetouh MI, Giovaneua BC. Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts.Anti-cancer Drugs. 1995, 6(1):83-95.
[58] Kumi Kawwno, Masato Watanabe, Tatsuhiro Yamamoto. Et al. Enahced antitumor effect of camptothecin loaded in long-circulatin polymeric micelles. Journal of Controlled Release. 2006, 112:329-332.
[59] Shicheng Yang, Jiabi Zhu, Yu Lu, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharmaceutical Research.1999, 16(5):751-757.
[60] Ertl B, Platzer P, Wirth M, et al. Poly(D,L-lactic-co-glycolic acid) microspheres for sustained delivery and stabilization of camptothecin.Journal of controlled release. 1999, 61(3):305-317.
[61] Tong W. Wang L, D'Souza MJ. Evaluation of PLGA microspheres as delivery system for antitumor agent camptothecin. Drug Dev Ind Pharm.2003, 29(7):745-756.
[62] Thomas Schluep, Jianjun Cheng, Kay T. Khim et al. Pharmacokenetics and biodistribution of the camptothecin-polymic conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemotheapy Pharmcology. 2006, 57:654-662.
[63] Anita Lalloo, Piyun Chao, Peidi Hu, et al. Pharmacokinetic and pharmcodynamic evaluation of a novel in situ forming poly(ethylene glycol)-based hydrogel for the controlled delivery of the camptothecin.Journal of Controlled Release. 2006, 112:333-342.
[1]Qing-Yong Li,Yuan-Gang Zu,Rong-Zhen Shi,et al.Review Camptothecin:current perspectives.Current Medicinal Chemistry[J].2006,13(17):2021-2039.
[2]Olivier Lavergne,Laurence Lesueur-Ginot,Francesc Pla Rodas,et al.Homocamptothecin:syntheisi and antitumor activity of novel E-ring-modifed camptothecin analogues.Journal of medicinal chemistry[J].1998,41:5410-5419.
[3]C.Kojima,K.Kono,K.Maruyama,et al.Synthesis of Polyamidoamine Dendrimers having Poly(ethyleneglycol) grafts and their ability to encapsulate anticancer drugs[J].Bioconjugate chemistry,2000,11:910-917.
[4]GF,Pan,Y.Lemmouchi,E.O.Akala,et al.Studies on PEGylated and drug-loaded PAMAM Dendrimers[J].Journal of Bioactive and Compatible Polymers.2005,20:113-128.
[5]Dan Luo,Kraig,Haverstick,Nadya Belcheva,Ernest Han,W.Mark Saltzman.Poly(ethylene glycol)-conjugated PAMAM Dendrimer for biocompatible,high-efficiency DNA delivery[J].Macromolecules,2002,35:3456-3462.
[6]D.Bhadra,S.Bhadra,S.Jain,N.K.Jain.A PEGylated dendritic nanoparticulate carrier of fluorouacil[J].International Journal of Pharmaceutics,2003,257:111-124.
[7]Rong-Qin Huang,Ying-Hua Qu,Wei-Lun Ke,Jian-Hua Zhu,Yuan-Ying Pei,Chen Jiang.Efficient gene delivery targeted to the brain using a transferring-conjugated polyethyleneglycol-modified polyamidoamine dendrimer[J].The FASEB Journal,2007,21:1117-1125.
[8]Michelle K Calabretta,Amit Kumar,Alison M.McDermott,Chengzhi Cai.Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups[J].Biomacromolecules,2007,(8):1807-1811.
[9]Samaresh Ghosh.Novel poly(ethylene glycol) embedded polyamidoamine side chain dendritic polyurethane architecture: synthesis and preliminary studies on the cytotoxicity and interaction with tryptophan molecule[J].Biomacromolecules. 2004. 5:1602-1605.
[10] Chie Kljima, Yoko Toi, Atsushi Harada, Kenji Kono. Preparation of poly(ethylene glycol) -attached dendrimers encapsulating photosensitizers for application to photodynamic therapy[J]. Bioconjugate chem.2007.18:663-670.
[11] Michelle K,Calabretta, Amit Kumar, Alison M. McDermott, Chengzhi CAI.Antibacterial activities of poly(amidoamine ) dendrimers terminated with amino and poly(ethylent glycol groups[J]. Biomacromolecules. 2007, 8:1807-1811.
[12] Tatsuya Okuda, Shigeru Kawakami, Tadahiro Maeie, Takuro Niidome,Fumiyoshi Yamashita, Mitsuru Hashida. Biodistubution characetristics of amino acid dendrimers and their PEGylated derivatives after intravenous dministration[J]. Journal of Controlled Release. 2006. 114:69-77.
[13] Gaur U, Sahoo SK, De TK, et al. Biodistribution of fluoresceinated dextran using novel nanoparticles evading reticuloendothelial system[J]. Int J Pharm,2000,202(1-2): 1-10.
[14] Duncan R, Connors TA, Meada H. Drug targeting in cancer therapy: the magic bullet, what next? [J] J Drug Target, 1996, 3(5): 317-319.
[15] Hua Lu, Haixia Lin, Yi Jiang, Xinguang Zhou, Beili Wu, et al. Synthesis and antitumor activity of 20-o-linked succinate-based camptothecin ester derivatives[J]. Letters in Drug Design & Discovery, 2006 ,3(2) :83-86.
[16] Tamar Minko, Pankaj V. Paranjpe, Bo Qiu, Anita Lalloo, Roney Won, Stanley Stein, Patrick J. Sinko. Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethyleneglycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cell[J]. Cancer Chemother Pharmacol, 2002, 50:143-150.
[17] Deshan Yu, Ping Peng, Sonia S. Dharap, Yang Wang, Mary Mehlig, Pooja Chandna, Hong Zhao, David Filpula, Karen Yang, Vima Borowski, Gerrit Borchard, Zhihua Zhang, Tamara Minko. Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo[J]. Journal of Controlled Release, 2005, 110:90-102.
[18]Pandaj V.Paranjpe,Yu Chen,Vladyslav Kholodovych,Willian Welsh,Stanley Stein,Patrick J.Sinko.Tumor-targeted bioconjugate based delivery of camptothecin:design,synthesis and in vitro evaluation[J].Journal of Controlled Release,2004,100:275-292.
[19]Jack W.Singer,Rama Bhatt,John Tulinkdy,Kent R.Buhler,Eveline Heasley,Peter Klein,Peter de Vris.Water-soluble poly-(L-glutamic acid)-Gly-camptothecin conjugates enhance camptothecin stability and efficacy in vivo[J].Journal of Controlled Release,2001,74:243-247.
[20]Thomas Schluep,Jianjun cheng,Kay T.Khin,Mark E.Davis.Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice[J]Cancer Chemother Pharmacol,2006,57:654-662.
[21]V.R.Caiolfa,M.Zamai,A.Fiorino,E.Frigerio,C.Pellizzoni,R.d'Argy,A.Ghiglieri,M.G.Castelli,M.Farao,E.Pesenti,M.Gigli,F.Angelucci,A.Suarato.Polymer-bound camptothecin:initial biodistribution and antiumor activity studies[J].Journal of Controlled Release,2000,65:105-119.
[22]Cheol Moon,Young Min Kwon,Won Kyu Lee,Yoon Jeong Park,Li Chien Chang,Victor C.Yang.A novel polyrotaxane-based intracellular delivery system for camptothecin:in vitro feasibility evaluation[J].Journal of Biomedical Materials Research Part A 2008,84(1):238-246.
[23]Yeh C-JG,Faulk WP.Killing of human tumor cells in culture with adriamycin conjugates of human transferrin[J].Clin Immunol Immunopathol.1984,32:1-11.
[24]Lai H,Sasaki T,Singh NP,et al.Effects of artemisinin-tagged holotransferrin on cancer cells[J].Life Sci,2005,76:1267-1279.
[25]Suzuki R,Takizawa T,Kuwata Y,et al.Effective antitumor activity of Oxaliplatin encapsulated in transferrin-PEG-liposome[J].Int J Pharm,2008,346(1-2):143-150.
[26]Kobayashi T,Ishida T,Okada Y,et al.Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells[J].Int J Pharm,2007,329(1-2):94-102.
[27]Sahoo SK,Labhasetwar V.Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J].Mol Pharm,2005,2(5):373-383.
[28]Abela RA,Qian J,Xu L,et al.Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells[J].Cancer Gene Ther,2008,15(8):496-507.
[29]Jiang YY,Liu C,Hong MH,et al.Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system:design,synthesis,and biological evaluation[J].Bioconjug Chem,2007,18(1):41-49.
[30]Hong MH,Zhu SJ,Jiang YY,Tang GT,Pei YY.Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin[J].Journal of Controlled Release.2009,133:96-102
[31]Mao H,Roy K,Troung-Le VL,et al.Chitosan-DNA nanoparticles as gene carriers:synthesis,characterization and transfection efficiency[J],J Control Release,2001,70:399-421.
[32]Citoles L,Ferreras M,Munoz R,et al.Targeting cancer cells with transferrin conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrinb or ebulin l[J].Cancer Letters,2002,184:29-35.
[33]Kursa M,Walker GF,Roessler V,et al.Novel shielded tranferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer[J].Bioconjugate Chem,2003,14:222-231.
[34]Wagner E,Zenke M,Cotton M,et al.Transferrin-polycation conjugates ascarriers for DNA uptake into cells[J].Biochemistry,1990,87(5):3410-3414.-27]
[35]Duncan R.J.S,Weston P.D,Wrigglesworth R.A new reagent which may be used to introduce sulfhydryl groups into proteins,and its use in the preparation of conjugates for immunoassay[J].Analytical Biochemistry,1983,132:68-73.
[36]Kratz F,Beyer U,Schumacher P,et al.Synthesis of new maleimide derivatives of daunorubicin and biological activity of acid labile transferrin conjugates[J].Bioorganic & Medicinal Chemistry Letters,1997,7(5):617-622.
[37]Ellman G.L.Tissue sulfhydryl groups[J].Archives of Biochemistry and Biophysics,1959,82:70-77.
[38]Antonio Quintana,Ewa Raczka,Lars Piehler,Inhan Lee,Andrzej Myc,Istvan Majoros,Anil K.Patri,Thommey Thomas,James Mule,James R.Baker,Jr.Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor[J]. Pharmceutical Research, 2002,19(9): 1310-1316.
[39] Youngseon Choi, Thommey Thomas, Alina Kotlyar, James R. Baker, Jr.Synthesis and functional evaluation of DNA-assembled Polyamidoamine Dendrimer clusters for cancer cell-specific targeting[J]. Chemistry and Biology, 2005,12:35-43.
[40] Mohamed, EI-Sayed, Mohammad F. Kiani, Mike D. Naimark, Ahmed H.Hikal, Hamidreza Ghandehari. Extravasation of Poly(amidoamine) (PAMAM) Dendrimers across microvascular network endothelium[J].Pharmaceutical Research, 18(1):23-28.
[41] Tsutomu Yasukawa, Hideya Kimura, Yasubiko Tabata, Hideki Miyamoto,Yosbibito Honda, Yosbito Ikada, Yuibciro Ogura. Targeted delivery of anti-angiogenic agent TNP-470 using water-soluble polymer in the treatment of choroidal neovascularization[J]. Investigative Ophthalmology & Visual Science, 1999, 40(11): 2690-2696.
[42] Heman Sarin, Ariel S Kanevsdy, Haitao Wu, Kyle R Brimacombe, Steve H Fung, Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells[J]. Journal of Translational Medicine. 2008. 6:80
[1]Jiang YY,Liu C,Hong MH,et al.Tumor cell targeting of transferrin-PEG TNF-alpha conjugate via a receptor-mediated delivery system:design,synthesis,and biological evaluation[J].Bioconjug Chem,2007,18(1):41-49
[2]Fritzer M,Barabas K,Sz(u|¨)ts V,et al.Cytotoxicity of a transferring-adriamycin conjugate to anthracycline-resistant cells[J].Int.J.Cancer,1992,52:619-623.
[3]Berczi A,Barabas K,Sizensky J.A.,et al.Adriamycin conjugates of human transferring bind transferring receptors and kill K562 and HL60 cells[J].Archives of Biochemistry and Biophysics,1993,300(1):356-363.
[4]D'Alessandro A.M.,D'Andrea G,Ciccio L.D.,et al.3'-Azido-3'-deoxythymidine reduces the rate of transferring receptorendocytosis in K562 cells[J].Biochimica et Biophsica Acta,1999,1450:232-241.
[5]Perez G,Garbossa G,Sassetti B,et al.Interference of aluminium on iron metabolism in erythroleukaemia K562 cells[J].Journal of InorganicBiochemistry,1999.76:105-112.
[6]Kircheis R,Blessing T,Brunner S,et al.Tumor targeting with surface-shielded ligand-polycation DNA complexes[J].Journal of Controlled release,2001,72:165-170.
[7]Fritzer M,Szekeres T,Sz(u|¨)ts V,et al.Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells[J].Biochemical Phamacology,1996,51:489-493.
[8]Tanaka T,Kaneo Y,Miyashita M.Synthesis of transferring-mitomycin C conjugate as a receptor-mediated drug targeting system[J].Bio Pharm Bull,1995,19(5):774-777.
[9]Maruyama K,Ishida O,Kasaoka S,et al.Intracellular targeting of sodium mercaptoundecahydrododecaborate(BSH) to solid tumors by transferring-PE liposomes,for boron nertron-capture therapy(BNCT)[J].Journal of Controlled release.2004,98:195-207.
[10]Voinea M,Dragomir E,Manduteanu I,et al.Binding and uptake of transferring-bound liposomes targeted to transferring receptors of endothelial cells[J].Vascular Pharmacology,2002,39:13-20.
[11]Citores L,Ferreras M,Munoz R,et al.Targeting cancer cells with transferring conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrinb or ebulin l[J].Cancer Letters,2002,184:29-35.
[12]Tanaka T,Miyashita SM,Kaneo YF.Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].International Journal of Pharmaceutics,2004,277:39-61.
[13]林溪,黄秀旺.人转铁蛋白-阿霉素结合物的制备及其体外细胞毒作用[J].肿瘤,2000,20(4):263-265.
[14]林溪,黄秀旺,柯丹如等.人转铁蛋白-甲氨喋呤结合物对人肝细胞、人肝癌细胞体外细胞毒的作用特点[J].福建医科大学学报,2001,35(1):7-9.
[15]Sahoo SK,Labhasetwar V.Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention[J].Mol Pharm,2005,2(5):373-383.
[16]Sorensen M,Sehested M,Jensen PB.Effect of cellular ATP depletion on topoisomerase Ⅱ poisons.Abrogation Of cleavable-complex formation by etoposide but not by amsacrine[J].Mol Pharmacol,1999,55(3):424-431.
[17]Mousavi SA,Malerod L,Berg T,et al.Clathrin-dependent endocytosis[J].Biochem J,2004,377:1-16.
[18]Fielding CJ,Fielding PE.Caveolae and intracellular trafficking of cholesterol [J].Adv Drug Deliv Rev,2001,49(3):251-264.
[19]Sieczkarski SB.Whittaker GR.Dissecting virus entry via endocytosis[J].J Gen Virol,2002,83:1535-1545.
[20]Gruenberg J.The endocytic pathway:a mosaic of domains[J].Nat Rev,Mol Cell Biol,2001,2(10):721-730.
[21]Casey CA,Wiegert RL,Tuma DJ.Effect of hyperosmolarity on both receptor-mediated and fluid-phase endocytosis in ethanol-fed animals[J].Biochem Pharmacol,1995,49:1117-1123.
[22]Chen J,Li G,Lu J,et al.A novel type of PTD,common helix-loop-helix motif,could efficiently mediate protein transduction into mammalian cells[J].Biochem Biophys Res Commun,2006,347:931-940.
[23]Schnitzer JE,Oh P,Pinney E,et al.Filipin-sensitive caveolar-mediated transport in endothelium:Reduced transcytosis,scavenger endocytosis,and capillary permeability of selected macromolecules[J].J Cell Biol,1994,127:1217-1232.
[24]Kheirolomoom A,Ferrara KW.Cholesterol transport from liposomal delivery vehicles[J].Biomaterials,2007,28:4311-4320.
[25]Kitchens KM,Kolhatkar RB,Swaan PW,et al.Endocytosis inhibitors prevent poly(amidoamine) dendrimer internalization and permeability across Caco-2cells[J].Mol Pharm,2008,5:364-369.
[26]Jevprasesphant R,Penny J,Attwood D,et al.Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity[J].Pharm Res,2003,20:1543-1550.
[27]Jiang S,Rhee SW,Gleeson PA,et al.Capacity of the Golgi Apparatus for Cargo Transport Prior to Complete Assembly[J].Mol Biol Cell,2006,17(9):4105-4117.
[28]Ruth Duncan,Lorella Izzo.Dendrimer biocompatibility and toxicity[J].Advanced drug delivey reviews.2005.57:2215-2237.
[29]Hui-ting Chen,Michael F.Neerman,Alan R.Parrish et al.Cytotoxicity, hemolysis,and acute in vivo toxicity fo dendrimers based on melamine,candidate vehicles for drug delivery[J].J.AM.CHEM.SOC.2004.126(32):10044-10048.
[30]aniels TR,Delgado T,Helguera G,et al.The transferrin receptor part Ⅱ:targeted delivery of therapeutic agents into cancer cells[J].Clin Immunol,2006,121:159-176.
[31]Li H,Sun H,Qian ZM.The role of the transferrin-transferrin-receptor system in drug delivery and targeting[J].Trends Pharmacol Sci,2002,23(5):206-209.
[32]Anabousi S,Bakowsky U,Schneider M,et al.In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer[J].Eur J Pharm Sci,2006,29:367-374.
[33]Xiangyang Wang,Xiang Zhou,Sidney M.Hecht.Role of the 20-hydroxyl group in camptothecin binding by the Topoisomerase 1-DNA binary complex[J].Biochemistry,1999,38:4374-4381.
[34]Beverly A.Teicher.Next generation topoisomerase 1 inhibitors rationale and biomarker strategies[J].Biochemical Pharmcology,2008,75:1262-1271.
[35]Andrew J.Hudson,Nadia Normand,John Ackroyd.Cellular delivery of hammerhead ribozymes conjugated to a transferrin receptor antibody[J].International Journal of Pharmaceutics.1999,182:49-58.
[36]Gabor F,Schwarzbauer A,Wirth M.Lectin-mediated drug delivery:binding and uptake of BSA-WGA conjugates using the Caco-2 model[J].Int J Pharm,2002,237(1-2):227-239.
[37]Hongyan Li,Zhongmimg Qian.Transferrin/transferring receptor-mediated drug delivery[J].Medicinal Research Reviews.2002,22(3):225-250.
[38]Ping-Shan Lai,P.-J.L.,Cheng-Liang Peng,Chin-Ling Pai,Wei-Nen Yen,Ming-Yi Huang,Tai-Horng Young,Ming-Jium Shieh.Doxorubin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy[J].Journal of Controlled Release 2007,(122):39-46.
[1] Thomas Schluep, Jianjun Cheng, Kay T. Khim et al. Pharmacokenetics and biodistribution of the camptothecin-polymet conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemotheapy Pharmcology. 2006, 57:654-662.
[2] Anita Lalloo, Piyun Chao, Peidi Hu, et al. Pharmacokinetic and pharmcodynamic evaluation of a novel in situ forming poly(ethylene glycol)-based hydrogel for the controlled delivery of the camptothecin. Journal of Controlled Release. 2006,112:333-342.
[3] Dennis O. Scott, Dilbir S. Bindra, Valentino J. Stella. Plasma pharmacokinetics of the lactone and carboxylate forms of 20(S)-camptothecin in anesthetized rats.Pharmaceutical Research. 1993, 10(10):1451-1457.
[4] Kumi Kawwno, Masato Watanabe, Tatsuhiro Yamamoto. Et al. Enahced antitumor effect of camptothecin loaded in long-circulatin polymeric micelles.Journal of Controlled Release. 2006, 112:329-332.
[5] Shicheng Yang, Jiabi Zhu, Yu Lu, et al. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharmaceutical Research. 1999,16(5):751-757.
[6] Tsutsumi Y, Kihira T, Tsunoda S, et al. Molecular design of hybrid tumor necrosis factor-αⅢ: polyethylene glycol-modified tumor necrosis factor-a has markedly enhanced antitumor potency due to long plasma half-life and higher tumor accumulate on. J Pharmacol Exp Ther. 1996,278:1006-1011.
[7] Imoto H, Sakamura Y, Ohkouchi K, et al. Disposition characteristics of macromoleules in the perfused tissue-isolated tumor preparation. Cancer Research. 1992, 52:4396-4401.
[8] Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting [J].Adv Enzyme Regul, 2001,41(1):189-207.
[9] Maeda H, Wu J, Sawa T, et al. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review [J]. J Control Release, 2000, 65(1-2):271-284.
[10] Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS [J]. J Control Release,2001,74(1-3):47-61.
[11] Tanaka T, Shiramoto S, Miyashita M, et al. Tumor targeting based on the effect of enhanced permeability and retention(EPR) and the mechanism of receptor-mediated endocytosis(RME)[J].Int J Pharm,2004,277(1-2):39-61.
[12]Greenwald RB.PEG drugs:an overview[J].J Control Release,2001,74(1-3):159-171.
[13]Shicheng Yang,Lifang Lu,Ying Cai,ea tl.Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.Journal of Controlled Release.1999,59:299-307
[14]Jultani A,Li C,Ozen M,et al.Paclitaxel and water-soluble poly(L-glutamic acid)- paclitaxel,induce direct chromosomal abnormalities and cell death in a murine metastatic melanoma cell line[J].Anticancer Res,1997,17:4269-4274.
[15]Zunino F,Giuliani F,Savi G,et al.Anti-tumor activity of Daunorubicin linked to poly-L-aspartic acid[J].Int J Cancer,1982,30:465-470.
[16]Greenwald RB,Choe YH,McGuire J,et al.Effective drug delivery by PEGylated drug conjugates[J].Adv Drug Deliv Rev,2003,55(2):217-250.
[17]Hong MH,Zhu SJ,Jiang YY,Tang GT,Pei YY.Efficient Tumor Targeting of Hydroxycamptothecin Loaded PEGylated Niosomes Modified with Transferrin.Journal of Controlled Release.2009,133:96-102
[18]XueMing Li,LiYan Ding,Yuanlong.Xu,et al.Targeted delivery of doxorubicin using stealth liposomes modified with transferrin.International Journal of Pharmaceutics.2009,373:116-126.
[19]Yu Gao,Lingli Chen,Wangwen Gu,et al.Targeted nanoassembly loaded with Docetaxel improves intracellular drug delivery and efficacy in murine breast cancer model.Molecular Pharmaceutics.2008,5:1044-1054.
[20]Masato Watanabe,Kumi Kawano,Kazunori Toma,et al.In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid human serum albumin.Journal of Controlled Release.2008,127:231-238.
[1]Namita S,Peter A.Ki67 structure,function and new antibodies[J]J Pathol,1992,168:161
[2]Marie C.Prewett,Andrea T.Hooper,Rajiv Bassi,et al.Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irrnotecan(CPT-11) against human colorectal tumor xenografts.Clinical Cancer Research.2002,8:994-1003.
[3]Ying Chau,Robert Padera,Natalie M.Dang,et al.Antitumor efficacy of a novel polymer-peptide-drug conjugate in human tumor xenograft models.Internation Journal of Cancer.2006,118:1519-1526.
[1]ESFAND R,TOMALIA DA.Poly(amidoamine)(PAMAM) dendrimers:from biomimicry to drug delivery and biomedical applications.Drug Discov Today,2001,6(8):427-436.
[2]GILLIES E R,FRECHET J M J.Dendrimers and dendritic polymers in drug delivery[J].Drug Discov Today,2005,10:35-43.
[3]ROBERTS J C,BHALGAT M K,ZERA R T.Preliminary biological evaluation of polyamidomine(PAMAM) Starbutst~(TM) dendrimers[J].J Biomed Mater Res,1996,30:53-65.
[4]JEVPRASESPHANT R,PENNY J,JALAL R,el al.The influence of surface modification on the cytotoxicity of PAMAM dendrimers[J].Int J Pharm,2003,(252):263-266.
[5]DOMANSKI D M,KLAJNERT B,BRYSZEWSKA M.Influence of PAMAM dendrimers on human red blood cells[J].Bioelectrochemistry,2004,63:189-191.
[6]EL-SAYED M,RHODS C A,G1NSKE M,et al.Transport mechanism of polyamidoamine dendrimers across Caco-2 cell monolayers[J],Int J Pharm,2003,(265):151-157.
[7]KOJIMA C,KONO K,MARUYAMA K,et al.Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs[J].Bioconjug Chem,2000,11(6):910-917.
[8]GURDAG S,KHANDARE J,STAPELS S,et al.Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and -resistant cell lines[J].Bioconjug Chem,2006,17:275-283.
[9]BHADRA D,BHADRA S,JAIN S,et al.A PEGylated dendritic anoparticulate carrier of fluorouracil[J].Int J Pharm,2003,(257):111-124.
[10]PAN G F LEMMOUCHI Y,EMMANUEL O,et al.Studies on PEGylated and drug-loaded PAMAM dendrimers[J].J Bioact Compat Pol,2005,20:113-128.
[11]KONDA S D,AREF M,WANG S,et al.Specific targeting of folate-dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts[J].Magnetic Resonance Materials in Physics,Biology and Medicine 2001,12:104-113.
[12]QUINTANA A,RACZKA E,PIEHLER L,et al.Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor[J].Pharm Res,2002,19(9):1310-1316.
[13]MAJOROS I J,THOMAS T P,MEHTA C B,et al.Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy[J].J Med Chem 2005,48(19):5892-5899
[14] THOMAS T P, MAJOROS I J, KOTLYAR A, et al. Targeting and inhibition of cell growth by an engineered dendritic nanodevice[J]. J Med Chem, 2005,48(11):3729-3735.
[15] PATUI A K, KUKOWSKA-LATALLO J F, BAKER JR J R, et al. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex[J]. Adv Drug Deliver Rev, 2005, 57:2203-2214.
[16] MAJOROS I J, MYC A, THOMAS T, et al. PAMAM dendrimer-based multifunctional for cancer therapy: synthesis, characterization, and founctionality[J]. Biomacromolecules, 2006,7(2) :572-579.
[17] SHUKLA S., WU G., CHATTERJEE M, et al. Synthesis and biological evaluation of folate receptor targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy[J]. Bioconjug. Chem., 2003, (14): 158-167.
[18] YANG W, BARTH F, WU G, et al. Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas[J]. Appl Radiat Isotopes, 2004,(61): 981-985.
[19] YANG H, LOPINA S T. In vitro enzymatic stability of dendritic peptides[J/OL]. J Biomed Mater Res, 2006, 76A(2), 398-407[2005-11-03]. http://www.iterscienct.wiley.com
[20] SAMHAROV D V, JIE A F, FILIPPOV D V, et al. Binding and retention of polycationic peptides and dendrimers in the vascular wall[J]. FEBS Lett. 2003, 537:6-10.
[21] SHUKLA R, THOMAS T P, PETERS J, et al. Tumor angiogenic vasculature targeting with PAMAM dendrimer-RGD conjugates[J]. Chem. Commun, 2005, 5739-5741.
[22] EICHMAN J D, BIELINSKA A U, KUKOWSKA-LATALLO J F, et al. The use of PAMAM dendrimers in the efficient transfer of genetic material into cells[J]. Pharmaceutical SCI &Technol Today, 2000, (3)7:232-245.
[23] BIELINSKA AU, CHEN C L, JOHNSON J, et al. DNA complexing with polyamidoamine dendrimers: implications for transfection[J]. Bioconjug Chem, 1999, 10:843-850.
[24]LUO D, HAVERSTICK K, BELCHEVA N, et al. Poly(ethylene glycol)-conjugated PAMAM dendrimer for biocompatible, high-efficiency DNA delivery[J]. Macromolecules,2002,35(9):3456-3462.
[25] MARUYAMA-TABATA H, HARADA Y, MATSUMURA T, et al. Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer[J].Gene Ther, 2000, 7(1):53-60.
[26] HOWARD DS, RIZZIERRI DA, GIMES B, et al. Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer[J]. Leukemia. 1999, 13(10): 1608-1616.
[27] HUDDE T, RAYNER SA, COMER RM, et al. Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium[J]. Gene Therapy, 1999,6:939-943.
[28] HUANG R Q, YANG W L, JIANG C, et al. Gene delivery into brain capillary endothelial cells using Antp-modified DNA-loaded nanoparticles[J]. Chem Pharm Bull 2006,54(9):1254-1258.
[29] HYUNMIN K, ROBERT DL, MICHAEL H F, et al. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides[J]. Pharm Res, 2005,22(12):201-2106.
[30] KIM J B, CHOI J S, NAM K, et al. Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg[J]. J Control Release, 2006,114:110-117.
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