纳米金棒靶向抗肿瘤的研究
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摘要
恶胜肿瘤严重危害着人类健康,人们称它是“20世纪的瘟疫”。肿瘤热疗已经成为继手术、放疗、化疗之后一种全新治疗肿瘤的新方法。由于其无毒副作用,不损伤人体正常组织,不破坏自身免疫力等优点,而备受人们的关注。热疗不但对肿瘤细胞有直接的细胞毒效应,还可以增强化疗、放疗的疗效,提高机体免疫力,抑制和预防癌症复发和转移。
本研究合成了纳米金棒材料,并进一步将可以特异性识别肝癌细胞的12肽连接在纳米金棒表面,连肽的纳米金棒材料具有较好的近红外吸收能力和良好的水溶性。
进一步考察了纳米金棒对HepG2细胞、BC-37细胞、A549细胞和Hela细胞的细胞毒性,试验结果表明纳米金棒在21.25μM-42.5μM浓度范围内对细胞的毒性较小;随后在合适的纳米金棒浓度下对肿瘤细胞进行红外照射,通过MTT比色法证明纳米金棒可抑制以上四种肿瘤细胞的增殖,抑制率均可达90%以上;连肽的纳米金棒对肝癌细胞的靶向抑制作用结果显示其对HepG2细胞有显著的抑制作用,抑制率可达90%左右,而在相同条件下对HL7702细胞和Hela细胞均未表现出明显的抑制作用。
最后对纳米金棒和连肽纳米金棒抑制小鼠实体瘤生长进行研究。以小鼠皮下接种肝癌细胞株H22为实体瘤模型,将纳米金棒和连肽纳米金棒材料原位注入小鼠瘤体处并进行红外照射后,纳米金棒的抑瘤率可达64%,连肽纳米金棒材料的抑瘤率可达70%。
Malignant tumor is serious harm to human health cancer, people called it a "plague of the 20th century." Cancer has become the number one killer of urban residents in China, second only to heart disease, cerebrovascular disease mortality caused. A recent UK study shows that in the next 40 years, the chances of human cancer, especially malignant tumor to double in the treatment of advanced cancer, the current through surgery, radiotherapy, chemotherapy, three means there has been a significant limitation , surgery, radiation therapy can not solve the problem of tumor cells in systemic metastasis, chemotherapy, although the effect rapidly, but can easily result in systemic toxicity.
Hyperthermia has been following the surgery, radiotherapy and chemotherapy treatment of cancer after a new method, the basic principle is to use physical energy heating the tumor tissue temperature to rise to the effective treatment temperature (41-47℃), and to maintain a certain time, the use of normal tissue and tumor cell tolerance to temperature differences, in order to achieve both the tumor cells, without damage to normal tissue for therapeutic purposes. Hyperthermia on tumor cells not only have a direct cytotoxic effect, but also can enhance chemotherapy, radiation therapy, improve immunity, suppression and prevention of cancer recurrence and metastasis.
However, in recent years with the development of nanotechnology, cancer treatment toward a more rational and more effective direction comprehensive treatment, including application of nanotechnology development with the overall treatment time plays an increasingly important position. The results show that gold nanoparticles have a strong in the near infrared region of light absorption, near infrared (800-1200 nm) is the transmission window of normal tissue, near infrared laser on the human body damage is minimal. Gold nanoparticles by near-infrared laser irradiation, metal nano-materials will absorb the light energy into heat, prompting local temperature within the range to kill tumor cells for therapeutic purposes. This technique can not be completely avoided surgery to remove the tumor and chemotherapy resistance aroused by such shortcomings, these advantages in the biomedical field it has a wide application prospect.
In this study, gold nanoparticles were synthesized rod material, and gold nanoparticles inhibits tumor hyperthermia infrared determination of cell growth and targeting infrared hyperthermia were studied.
1 Seed growth method using the PEG modification of the successful synthesis of two kinds of nano materials, gold nanorods, and further modified gold nanoparticles targeting rods. nanorods are about to 40nm, a width of 12nm. The above two materials are strong infrared absorption and good stability.
2 MTT colorimetric assay on PEG modified gold nanorods HepG2, BC-37, A-549, Hela cell toxicity, the results shown in HepG2 cells on gold nanorods in 21.25μM, on the BC-37 and A-549 cells were In 28.3μM, on Hela cells in 42.5μM concentrations compared with the control group no significant difference in the cell is non-toxic, is the appropriate role of concentration. The targeting peptide modified gold nanoparticles on the rods on HepG2 cells in 5.31μM this is non-toxic concentrations, is the appropriate role of concentration.
3 PEG modification of the gold nanorod infrared hyperthermia effect on HepG2, BC-37, A-549, Hela cells, by cell viability test results show that gold nanoparticles infrared hyperthermia inhibited tumor cell proliferation, cell death rate was over 90%.Under an inverted microscope and cell morphology was observed after staining showed that the appropriate exposure conditions, the infrared hyperthermia the cells became round and the cytoplasm less contact with the surrounding cell disruption and cell adhesion reduce the features of apoptosis may occur.
4 Targeting peptide modified gold nanoparticles by infrared hyperthermia rod HepG2 hepatoma cells and normal liver cells HL7702, through MTT test showed that gold nanoparticles could inhibit the above two kinds of infrared hyperthermia cell proliferation, and the inhibition of power and infrared radiation was dependent relationship, with the irradiation power increases, cell viability decreased. The results show that the thermal sensitivity of HepG2 hepatoma cells was significantly higher than normal liver cells HL7702. Then modified gold nanoparticles targeting peptide rods on liver cancer cells HepG2, normal liver cells and Hela cells HL7702 infrared hyperthermia, experimental results show that the power 15W/cm2 on HepG2 cells was significantly inhibited, the inhibition rate of 90 %, while on HL7702 cells, Hela cells did not show significant inhibition, and the targeting peptide is not connected in the power of nano-gold bars under the infrared irradiation inhibition of HepG2 cells less than 5%.
5 Through the tail vein injection of different concentrations of PEG-nanorod measured obtaining the LD50 in mice was 0.71mg/kg.This experiment, mice injected with the concentration will not lead to death.WP05 modified nanorods were verified in vivo targeting, the effect was that gold nanoparticles modified infrared targeting tumor hyperthermia in the shows to a good prospect.
In summary, we successfully synthesized modified peptides in PEG and targeting materials, nano-gold bars, the two materials are strong infrared absorption and good stability, and its hydrosol also has good stability, their cell toxicity, has good biocompatibility and so on. And its inhibition of cell growth were determined, the results showed that gold nanoparticles infrared hyperthermia inhibited the growth of tumor cells, the maximum inhibition rate of 90% or more. Targeting Infrared hyperthermia and in vitro carried out a preliminary study. Therefore, this study may be cancer and other solid tumors provides a new way to targeted therapy. For later preparation of nano-materials, nano-particle surface modification of materials selection of molecular, nano-materials, the residue after treatment and the impact on normal tissue provides a theoretical basis for the gold nanoparticles infrared hyperthermia treatment of cancer clinical research a new idea.
本研究合成了纳米金棒材料,并进一步将可以特异性识别肝癌细胞的12肽连接在纳米金棒表面,连肽的纳米金棒材料具有较好的近红外吸收能力和良好的水溶性。
进一步考察了纳米金棒对HepG2细胞、BC-37细胞、A549细胞和Hela细胞的细胞毒性,试验结果表明纳米金棒在21.25μM-42.5μM浓度范围内对细胞的毒性较小;随后在合适的纳米金棒浓度下对肿瘤细胞进行红外照射,通过MTT比色法证明纳米金棒可抑制以上四种肿瘤细胞的增殖,抑制率均可达90%以上;连肽的纳米金棒对肝癌细胞的靶向抑制作用结果显示其对HepG2细胞有显著的抑制作用,抑制率可达90%左右,而在相同条件下对HL7702细胞和Hela细胞均未表现出明显的抑制作用。
最后对纳米金棒和连肽纳米金棒抑制小鼠实体瘤生长进行研究。以小鼠皮下接种肝癌细胞株H22为实体瘤模型,将纳米金棒和连肽纳米金棒材料原位注入小鼠瘤体处并进行红外照射后,纳米金棒的抑瘤率可达64%,连肽纳米金棒材料的抑瘤率可达70%。
Malignant tumor is serious harm to human health cancer, people called it a "plague of the 20th century." Cancer has become the number one killer of urban residents in China, second only to heart disease, cerebrovascular disease mortality caused. A recent UK study shows that in the next 40 years, the chances of human cancer, especially malignant tumor to double in the treatment of advanced cancer, the current through surgery, radiotherapy, chemotherapy, three means there has been a significant limitation , surgery, radiation therapy can not solve the problem of tumor cells in systemic metastasis, chemotherapy, although the effect rapidly, but can easily result in systemic toxicity.
Hyperthermia has been following the surgery, radiotherapy and chemotherapy treatment of cancer after a new method, the basic principle is to use physical energy heating the tumor tissue temperature to rise to the effective treatment temperature (41-47℃), and to maintain a certain time, the use of normal tissue and tumor cell tolerance to temperature differences, in order to achieve both the tumor cells, without damage to normal tissue for therapeutic purposes. Hyperthermia on tumor cells not only have a direct cytotoxic effect, but also can enhance chemotherapy, radiation therapy, improve immunity, suppression and prevention of cancer recurrence and metastasis.
However, in recent years with the development of nanotechnology, cancer treatment toward a more rational and more effective direction comprehensive treatment, including application of nanotechnology development with the overall treatment time plays an increasingly important position. The results show that gold nanoparticles have a strong in the near infrared region of light absorption, near infrared (800-1200 nm) is the transmission window of normal tissue, near infrared laser on the human body damage is minimal. Gold nanoparticles by near-infrared laser irradiation, metal nano-materials will absorb the light energy into heat, prompting local temperature within the range to kill tumor cells for therapeutic purposes. This technique can not be completely avoided surgery to remove the tumor and chemotherapy resistance aroused by such shortcomings, these advantages in the biomedical field it has a wide application prospect.
In this study, gold nanoparticles were synthesized rod material, and gold nanoparticles inhibits tumor hyperthermia infrared determination of cell growth and targeting infrared hyperthermia were studied.
1 Seed growth method using the PEG modification of the successful synthesis of two kinds of nano materials, gold nanorods, and further modified gold nanoparticles targeting rods. nanorods are about to 40nm, a width of 12nm. The above two materials are strong infrared absorption and good stability.
2 MTT colorimetric assay on PEG modified gold nanorods HepG2, BC-37, A-549, Hela cell toxicity, the results shown in HepG2 cells on gold nanorods in 21.25μM, on the BC-37 and A-549 cells were In 28.3μM, on Hela cells in 42.5μM concentrations compared with the control group no significant difference in the cell is non-toxic, is the appropriate role of concentration. The targeting peptide modified gold nanoparticles on the rods on HepG2 cells in 5.31μM this is non-toxic concentrations, is the appropriate role of concentration.
3 PEG modification of the gold nanorod infrared hyperthermia effect on HepG2, BC-37, A-549, Hela cells, by cell viability test results show that gold nanoparticles infrared hyperthermia inhibited tumor cell proliferation, cell death rate was over 90%.Under an inverted microscope and cell morphology was observed after staining showed that the appropriate exposure conditions, the infrared hyperthermia the cells became round and the cytoplasm less contact with the surrounding cell disruption and cell adhesion reduce the features of apoptosis may occur.
4 Targeting peptide modified gold nanoparticles by infrared hyperthermia rod HepG2 hepatoma cells and normal liver cells HL7702, through MTT test showed that gold nanoparticles could inhibit the above two kinds of infrared hyperthermia cell proliferation, and the inhibition of power and infrared radiation was dependent relationship, with the irradiation power increases, cell viability decreased. The results show that the thermal sensitivity of HepG2 hepatoma cells was significantly higher than normal liver cells HL7702. Then modified gold nanoparticles targeting peptide rods on liver cancer cells HepG2, normal liver cells and Hela cells HL7702 infrared hyperthermia, experimental results show that the power 15W/cm2 on HepG2 cells was significantly inhibited, the inhibition rate of 90 %, while on HL7702 cells, Hela cells did not show significant inhibition, and the targeting peptide is not connected in the power of nano-gold bars under the infrared irradiation inhibition of HepG2 cells less than 5%.
5 Through the tail vein injection of different concentrations of PEG-nanorod measured obtaining the LD50 in mice was 0.71mg/kg.This experiment, mice injected with the concentration will not lead to death.WP05 modified nanorods were verified in vivo targeting, the effect was that gold nanoparticles modified infrared targeting tumor hyperthermia in the shows to a good prospect.
In summary, we successfully synthesized modified peptides in PEG and targeting materials, nano-gold bars, the two materials are strong infrared absorption and good stability, and its hydrosol also has good stability, their cell toxicity, has good biocompatibility and so on. And its inhibition of cell growth were determined, the results showed that gold nanoparticles infrared hyperthermia inhibited the growth of tumor cells, the maximum inhibition rate of 90% or more. Targeting Infrared hyperthermia and in vitro carried out a preliminary study. Therefore, this study may be cancer and other solid tumors provides a new way to targeted therapy. For later preparation of nano-materials, nano-particle surface modification of materials selection of molecular, nano-materials, the residue after treatment and the impact on normal tissue provides a theoretical basis for the gold nanoparticles infrared hyperthermia treatment of cancer clinical research a new idea.
引文
[1] Kristine Novak(2003)Heating things up. Nature Review3:887
[2]癌性疲乏的研究现状(2006)《实用癌症杂志》04期
[3] Breasted JH (1930) The Edwin Smith surgical papyrus, vol1.University of Chicago
[4] Gazelle GS,Goldberg SN,Livraghi T,Solbiati L (2000) Tumorablation with radio-frequency energy. Radiology (Easton, Pa.) 217:633–646
[5] GoldBerg SN (2001) Radio frequency tumor ablation: principlesand techniques. Eur J Ultrasound 13(2):129-147
[6] Goldberg SN,Dupuy DE (2001) Image-guided radiofrequencytumor ablation: challenges and opportunities-part I. J VascInterv Radiol 12:1021–1032
[7] Seegenschmiedt MH, Brady LW, Sauer R (1990) Interstitialthermoradiotherapy: review on technical and clinical aspects. Am J Clin Oncol 13(4):352–363
[8] Urano M, Douple E (1992) Physics of microwave hyperthermiain hyperthermia and oncology, vol 3. Springer, Utrecht, The Netherlands, pp 11–98
[9] Sato M, Watanabe Y, Ueda S, Iseki S, Abe Y, Sato N, Kimura S, Okubo K, Onji M (1996) Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 110(5):1507–1514
[10] Kremkau FW (1979) Cancer therapy with ultrasound: a historical review. J Clin Ultrasound 7(4):287–300
[11] Huber P, Debus J, Jenne J, Jochle K, van Kaick G, Lorenz WJ, Wannenmacher M (1996) Therapeutic ultrasound in tumor therapy. Principles, applications and new development. Radiologe36(1):64–71
[12] Wu F, Chen WZ, Bai J, Zou JZ, Wang ZL, Zhu H, Wang ZB (2001) Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. Ultrasound Med Biol 27(8):1099–1106
[13] Svaasand LO, Gomer CJ, Morinelli E (1990) On the physical rationale of laser induced hyperthermia. Lasers Med Sci 5:121–128
[14] Yatvin MB,Dennis WH,et al.Sensitivity of tumor cells to heat and ways of modifying the response[J].Symp Soc Exp Biol ,1987,41:235-67
[15] Weian Zhao , Jefrey M. Karp(2009)Nanoantennas heat up. Nature Materials8:453-454
[16] Leith JT,et al.Hyperthermia potentiation biological aspects and application toradiation therapy[J].Cancer,1977,39:776
[17]魏宝清.放射生物学与放射治疗学[J].国外医学参考资料(肿瘤分册),1979,(2):53-59
[18]李振权.现代癌症治疗的趋势[J].国外医学参考资料(肿瘤分册),1979,(1):23
[19] El-Sayed MA (2001) Some interesting properties of metals confined in time and nanometer space of different shapes. Acc Chem Res 34:257–264
[20] Niemeyer CM (2001) Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science. Angew Chem Int Ed Engl 40:4128–4158
[21] Daniel MC, Astruc D (2004) Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104:293–346
[22] West JL, Halas NJ (2003) Engineered nanomaterials for biophotonics applications: improving sensing, imaging, andtherapeutics. Annu Rev Biomed Eng 5:285–292
[23] Xia Y, Halas NJ (2005) Shape-controlled synthesis and surface plasmonic properties of metallic nanostructures. MRS Bull 30:338–348
[24] Warren CWC, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S (2002) Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 13:40–46
[25] Parak WJ, Gerion D, Pellegrino T, Zanchet D, Micheel C, Williams SC, Boudreau R, Le Gros MA, Larabell CA, Alivisatos AP (2003) Biological applications of colloidal nanocrystals. Nanotechnology 14:R15–R27
[26] Katz E, Willner I (2004) Integrated nanoparticle-biomolecule hybrid systems: Synthesis, properties, and applications. Angew Chem Int Ed 43:6042–6108
[27] Pitsillides CM, Joe EK, Wei X, Anderson RR, Lin CP (2003) Selective cell targeting with light-absorbing microparticles and nanoparticles. Biophys J 84:4023–4032
[28] Zharov VP, Galitovsky V, Viegas M (2003) Photothermal detection of local thermal effects during selective nanophotothermolysis. Appl Phys Lett 83(24):4897–4899
[29] Zharov VP, Galitovskaya E, Viegas M (2004) Photothermal guidance for selective photothermolysis with nanoparticles. Proc SPIE 5319:291–300
[30] Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:N309–N315
[31] Zharov VP, Galitovskaya EN, Johnson C, Kelly T (2005) Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy. Lasers Surg Med 37:219–226
[32] El-Sayed IH, Huang X, El-Sayed MA (2006) Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. Cancer Lett 239(1):129–135
[33] Huang X, Jain PK, El-Sayed IH, El-Sayed MA (2006) Determination of the minimum temperature required for selective photothermal destruction of cancer cells using immunotargeted gold nanoparticles. Photochem Photobiol 82(2):412–417
[34] Khlebtsov B, Zharov V, Melnikov A, Tuchin V, Khlebtsov N (2006) Optical amplification of photothermal therapy with gold nanoparticles and nanoclusters. Nanotechnology 17:5167–5179
[35] Huang X, El-Sayed IH, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128(6):2115–2120
[36] Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006) Gold nanorod-sensitized cell death: Microscopic observation of single living cells irradiated by pulsed near-infrared laser light in the presence of gold nanorods. Chem Lett 35(5):500–501
[37] Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006) Photothermal reshaping of gold nanorods prevents further cell death. Nanotechnology 17:4431–4435
[38] Huff TB, Tong L, Zhao Y, Hansen MN, Cheng JX, Wei A (2007) Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2(1):125–132
[39] Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Price RE, Hazle JD, Halas NJ, West JL (2003) Nanoshell-mediated near infrared thermal therapy of tumors under MR Guidance. Proc Natl Acad Sci 100:13549–13554
[40] Loo CH, Lin A, Hirsch LR, Lee MH, Barton J, Halas NJ, West J, Drezek RA (2004) Nanoshell-enabled photonics-based imagingand therapy of cancer. Tech Cancer Res Treat 3:33–40
[41] O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL (2004) Photothermal tumorablation in mice using near infrared absorbing nanoshells. Cancer Lett 209:171–176
[42] Loo C, Lowery A, Halas NJ, West JL, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711
[43] Chen J, Wiley B, Li ZY, Campbell D, Saeki F, Cang H, Au L, Lee J, Li X, Xie Y (2005) Gold nanocages: engineering their structure for biomedical applications. Adv Mater 17:2255–2261
[44] Hu M, Petrova H, Chen J, McLellan JM, Siekkinen AR, Marquez M, Li X, Xia Y, Hartland GV (2006) Ultrafast laser studies of the photothermal properties of gold nanocages. J PhysChem B 110(4):1520–1524
[45] Shi Kam NW, O’Connell M, Wisdom JA, Dai H (2005) Carbon nanotubes as multifunctional biological transporters and nearinfrared agents for selective cancer cell destruction. Proc Natl Acad Sci 102(33):11600–11605Moylan.DJ,et al.Hyperthermia:Scientific basis and clinical applications [M]. Therapeutic Radiology,Second Edition,1989,531
[46] Maltzahn G, Park J-H, Agrawal A, Bandaru NK, Das SK, SailorMJ, et al. Computationally cuided photothermal tumor therapusing long-circulating gold nanorod antennas. Cancer Res. 2009;69:3892–9.
[47] Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Halas NJ. Nanoshell-mediated near-infrared thermal therapy of tumorsunder magnetic resonance guidance. Proc Natl Acad Sci. 2003; 100:13549–54.
[48] Gobin AM, Lee MH, Halas NJ, James WD. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 2007;7:1929–34.
[49] Duff DG, Baiker A. A new hydrosol of gold clusters. 1. Formation and particle size variation. Langmuir. 1993;9:2301–9.
[50] Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor specific nanoparticle delivery: effect of particle size. Cancer Res. 2000;60:4440–5.
[51] Link S, El-Sayed MA (1999) Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. J Phys Chem B 103:4212–4217
[52] Nikoobakht B, El-Sayed MA (2003) Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem Mater 15:1957–1962
[53] Gobin AM, O’Neal DP, Watkins DM, Halas NJ, Drezek RA, West JL. Near infrared laser-tissue welding using nanoshells as an exogenous absorber. LasersSurg Med. 2005;9999:1–7.
[54] O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. Photothermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett. 2004;209:171–6.
[55] Hashizume H, Baluk P, Morikawa S, McLean JW. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000;156:1363–80.
[56] Loo C, Lowery A, Halas NJ, West JL, Drezek R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 2005;5:709–11.
[57] Lowery AR, Gobin AM, Day ES, Halas NJ, West JL. Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomed. 2006;1:149–54.
[58] Lin AWH, Lewinski NA, West JL. Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells. J Biomed Opt. 2005;10:064035-1-10.
[59] Diagaradjane P, Shetty A, Wang JC, Elliott AM, Schwartz J, Shentu S, et al. Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an integrated antihypoxic and localized vascular disrupting targeting strategy. Nano Lett. 2008;8:1492–500.
[60] Liao H, Hafner JH (2005) Gold nanorod bioconjugates. Chem Mater 17:4636–4641
[61] Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, Katayama Y, Niidome Y (2006) PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release 114:343–347
[62] Maeda H (2001) The enhanced permeability and Retention (EPR) effect in tumor Vasculature: the key role of Tumorselective macromolecular drug targeting. Adv Enzyme Regul 41:189–207
[63] Maedaa H, Fanga J, Inutsukaa T, Kitamoto Y (2003) Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int Immunopharmacol 3:319–328
[64] Fang J, Sawa T, Maeda H (2003) Factors and mechanism of“EPR”effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv Exp Med Biol 519:29–49
[65] Paciotti GF, Myer L, Weinreich D, Goia D, Pavel N, McLaughlin RE, Tamarkin L (2004) Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv 11:169–183
[66] Greish K, Sawa T, Fang J, Akaike T, Maeda H (2004) SMAdoxorubicin, a new polymeric micellar drug for effective targeting to solid tumors. J Control Release 97:219–230
[67] McNeil SE (2005) Nanotechnology for the biologist. J Leukoc Biol 78:585–594
[68] Kommareddy S, Amiji M (2007) Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice. J Pharm Sci 96(2):397–407
[69] Pissuwan D, Valenzuela SM, Cortie MB (2006) Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends Biotech 24(2):62–67
[70] Sokolov K, Follen M, Aaron J, Pavlova I, Malpica A, Lotan R, Richards-Kortum R (2003) Real-time vital optical imaging of precancer using anti–epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Res 63:1999–2004
[71] Sokolov K, Aaron J, Hsu B, Nida D, Gillanwater A, Follen M, Macaulay C, Adler-Storthz K, Korgel B, Discour M, Pasqualini R, Arap W, Lam W, Richartz-Kortum R (2003) Optical systems for in vivo molecular imaging of cancer. Technol Cancer Res Treat 2(6):491–504
[72] Hayat MA (1989) Colloidal gold: principles, methods and applications, vol 1 edn. Academic, San Diego
[73] El-Sayed IH, Huang X, El-Sayed MA (2005) Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett 5:829–834
[74] Leamon CP, Low PS (2001) Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discov Today 6:44–51
[75] Nayak S, Lee H, Chmielewski J, Lyon LA (2004) Folatemediated cell targeting and cytotoxicity using thermoresponsive microgels. J Am Chem Soc 126:10258–10259
[76] Robins HI,Grosen E,Katschinski DM,et al.Whole body hyperthermia induction of soluble tumor necrosis factor receptor:implications for rtheumatoid disease[J].J Rheumatol,1999,26(12):2513-2516
[77] Dixit V, Bossche JV, Sherman DM, Thompson DH. Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjugate Chem. 2006;17:603–9.
[78] Xiaohua Huang,Prashant K. Jain,Ivan H. El-Sayed,Mostafa A.El-Sayed .Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers Med Sci (2008) 23:217–228
[79] Dixit V, Bossche JV, Sherman DM, Thompson DH. Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjugate Chem. 2006;17:603–9.
[80] Wang SN, Deng YH, Xu H, Wu HB, Qiu YK, Chen DW. Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin. Eur J Pharma Biopharma. 2006;62:32–8.
[81] Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998;351:417–8.
[82] Yang Y, Jiang J-S, Du B, Gan Z-F, Qian M, Zhang P. Preparation and properties of a novel drug delivery system with both magnetic and biomolecular targeting. J Mater Sci Mater Med. 2009;20:301–7.
[83] J. Perez-Juste, L. M. Liz-Marzan, S. Carnie, D. Y. C. Chan, P. Mulvaney,Adv. Funct. Mater. 2004, 14, 571– 579.
[84] F. Kim, J. H. Song, P. D. Yang, J. Am. Chem. Soc. 2002, 124, 14316–14317.
[85] C. J. Johnson, E. Dujardin, S. A. Davis, C. J. Murphy, S. Mann, J. Mater. Chem. 2002, 12, 1765–1770
[86] J. Perez-Juste, I. Pastoriza-Santos, L. M. Liz-Marzan, P. Mulvaney, Coord. Chem. Rev. 2005, 249, 1870–1901.
[87]潘碧峰,崔大祥,徐萍,李清,黄拓,陈浩.种子生长法制备长径比为2.5的金纳米棒.材料科学与工程学报,2007,25,(3).
[88]裴立宅.表面活性剂在合成金纳米晶溶胶中的应用[J].稀有金属快报,2004,23(11): 35-38.
[89] T Yonezawa,T Kunitake.Practical preparation of anionic mercaptoligand-tablized gold nanoparticles and their immobilization[J].Colloids Surf A, l999, l49(1-3): l93-l99.
[90] M K Kim,Y M Jeon,W S Jeon,et a1.Novel dendronstabilized gold nanoparticles with high stability and narrow size distribution[J].Chem Commun,200l,5(7):667- 668.
[91] Pham T, Jackson JB, Halas NJ, Lee TR. Preparation and characterization of gold nanoshells coated with self-assembled monolayers. Langmuir. 2002;18:4915–20.
[92] Wang YJ, Zhu SG, Xun CF. Biochemistry. 3rd ed. Beijing, China: Higher Education Press; 2003.
[93] Fuente JM, Berry CC, Riehle MO. Nanoparticle targeting at cells. Langmuir. 2006;22:3286–93.
[94] Chen JY, Saeki F, Wiley BJ. Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 2005;5:473–7.
[95]牛建丽.纳米金红外热疗诱导肿瘤细胞凋亡的研究.2009
[96] Shun-Ying Liu .Zhong-Shi Liang .Feng Gao.Shu-Fang Luo. Guo-Quan Lu. In vitro photothermal study of gold nanoshells functionalized with small targeting peptides to liver cancer cells. J Mater Sci: Mater Med DOI 10.1007/s10856-009-3895-x.
[97] Huiyu Liu, Dong Chen, Fangqiong Tang, Gangjun Du, Linlin Li, Xianwei Meng, Wei Liang, Yangde Zhang, Xu Teng and Yi Li.Photothermal therapy of Lewis lungcarcinoma in mice using gold nanoshellson carboxylated polystyrene spheres. Nanotechnology 19,(2008) ,455101 (7pp)
[2]癌性疲乏的研究现状(2006)《实用癌症杂志》04期
[3] Breasted JH (1930) The Edwin Smith surgical papyrus, vol1.University of Chicago
[4] Gazelle GS,Goldberg SN,Livraghi T,Solbiati L (2000) Tumorablation with radio-frequency energy. Radiology (Easton, Pa.) 217:633–646
[5] GoldBerg SN (2001) Radio frequency tumor ablation: principlesand techniques. Eur J Ultrasound 13(2):129-147
[6] Goldberg SN,Dupuy DE (2001) Image-guided radiofrequencytumor ablation: challenges and opportunities-part I. J VascInterv Radiol 12:1021–1032
[7] Seegenschmiedt MH, Brady LW, Sauer R (1990) Interstitialthermoradiotherapy: review on technical and clinical aspects. Am J Clin Oncol 13(4):352–363
[8] Urano M, Douple E (1992) Physics of microwave hyperthermiain hyperthermia and oncology, vol 3. Springer, Utrecht, The Netherlands, pp 11–98
[9] Sato M, Watanabe Y, Ueda S, Iseki S, Abe Y, Sato N, Kimura S, Okubo K, Onji M (1996) Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 110(5):1507–1514
[10] Kremkau FW (1979) Cancer therapy with ultrasound: a historical review. J Clin Ultrasound 7(4):287–300
[11] Huber P, Debus J, Jenne J, Jochle K, van Kaick G, Lorenz WJ, Wannenmacher M (1996) Therapeutic ultrasound in tumor therapy. Principles, applications and new development. Radiologe36(1):64–71
[12] Wu F, Chen WZ, Bai J, Zou JZ, Wang ZL, Zhu H, Wang ZB (2001) Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. Ultrasound Med Biol 27(8):1099–1106
[13] Svaasand LO, Gomer CJ, Morinelli E (1990) On the physical rationale of laser induced hyperthermia. Lasers Med Sci 5:121–128
[14] Yatvin MB,Dennis WH,et al.Sensitivity of tumor cells to heat and ways of modifying the response[J].Symp Soc Exp Biol ,1987,41:235-67
[15] Weian Zhao , Jefrey M. Karp(2009)Nanoantennas heat up. Nature Materials8:453-454
[16] Leith JT,et al.Hyperthermia potentiation biological aspects and application toradiation therapy[J].Cancer,1977,39:776
[17]魏宝清.放射生物学与放射治疗学[J].国外医学参考资料(肿瘤分册),1979,(2):53-59
[18]李振权.现代癌症治疗的趋势[J].国外医学参考资料(肿瘤分册),1979,(1):23
[19] El-Sayed MA (2001) Some interesting properties of metals confined in time and nanometer space of different shapes. Acc Chem Res 34:257–264
[20] Niemeyer CM (2001) Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science. Angew Chem Int Ed Engl 40:4128–4158
[21] Daniel MC, Astruc D (2004) Gold nanoparticles: Assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104:293–346
[22] West JL, Halas NJ (2003) Engineered nanomaterials for biophotonics applications: improving sensing, imaging, andtherapeutics. Annu Rev Biomed Eng 5:285–292
[23] Xia Y, Halas NJ (2005) Shape-controlled synthesis and surface plasmonic properties of metallic nanostructures. MRS Bull 30:338–348
[24] Warren CWC, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S (2002) Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 13:40–46
[25] Parak WJ, Gerion D, Pellegrino T, Zanchet D, Micheel C, Williams SC, Boudreau R, Le Gros MA, Larabell CA, Alivisatos AP (2003) Biological applications of colloidal nanocrystals. Nanotechnology 14:R15–R27
[26] Katz E, Willner I (2004) Integrated nanoparticle-biomolecule hybrid systems: Synthesis, properties, and applications. Angew Chem Int Ed 43:6042–6108
[27] Pitsillides CM, Joe EK, Wei X, Anderson RR, Lin CP (2003) Selective cell targeting with light-absorbing microparticles and nanoparticles. Biophys J 84:4023–4032
[28] Zharov VP, Galitovsky V, Viegas M (2003) Photothermal detection of local thermal effects during selective nanophotothermolysis. Appl Phys Lett 83(24):4897–4899
[29] Zharov VP, Galitovskaya E, Viegas M (2004) Photothermal guidance for selective photothermolysis with nanoparticles. Proc SPIE 5319:291–300
[30] Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:N309–N315
[31] Zharov VP, Galitovskaya EN, Johnson C, Kelly T (2005) Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy. Lasers Surg Med 37:219–226
[32] El-Sayed IH, Huang X, El-Sayed MA (2006) Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. Cancer Lett 239(1):129–135
[33] Huang X, Jain PK, El-Sayed IH, El-Sayed MA (2006) Determination of the minimum temperature required for selective photothermal destruction of cancer cells using immunotargeted gold nanoparticles. Photochem Photobiol 82(2):412–417
[34] Khlebtsov B, Zharov V, Melnikov A, Tuchin V, Khlebtsov N (2006) Optical amplification of photothermal therapy with gold nanoparticles and nanoclusters. Nanotechnology 17:5167–5179
[35] Huang X, El-Sayed IH, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128(6):2115–2120
[36] Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006) Gold nanorod-sensitized cell death: Microscopic observation of single living cells irradiated by pulsed near-infrared laser light in the presence of gold nanorods. Chem Lett 35(5):500–501
[37] Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006) Photothermal reshaping of gold nanorods prevents further cell death. Nanotechnology 17:4431–4435
[38] Huff TB, Tong L, Zhao Y, Hansen MN, Cheng JX, Wei A (2007) Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2(1):125–132
[39] Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Price RE, Hazle JD, Halas NJ, West JL (2003) Nanoshell-mediated near infrared thermal therapy of tumors under MR Guidance. Proc Natl Acad Sci 100:13549–13554
[40] Loo CH, Lin A, Hirsch LR, Lee MH, Barton J, Halas NJ, West J, Drezek RA (2004) Nanoshell-enabled photonics-based imagingand therapy of cancer. Tech Cancer Res Treat 3:33–40
[41] O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL (2004) Photothermal tumorablation in mice using near infrared absorbing nanoshells. Cancer Lett 209:171–176
[42] Loo C, Lowery A, Halas NJ, West JL, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711
[43] Chen J, Wiley B, Li ZY, Campbell D, Saeki F, Cang H, Au L, Lee J, Li X, Xie Y (2005) Gold nanocages: engineering their structure for biomedical applications. Adv Mater 17:2255–2261
[44] Hu M, Petrova H, Chen J, McLellan JM, Siekkinen AR, Marquez M, Li X, Xia Y, Hartland GV (2006) Ultrafast laser studies of the photothermal properties of gold nanocages. J PhysChem B 110(4):1520–1524
[45] Shi Kam NW, O’Connell M, Wisdom JA, Dai H (2005) Carbon nanotubes as multifunctional biological transporters and nearinfrared agents for selective cancer cell destruction. Proc Natl Acad Sci 102(33):11600–11605Moylan.DJ,et al.Hyperthermia:Scientific basis and clinical applications [M]. Therapeutic Radiology,Second Edition,1989,531
[46] Maltzahn G, Park J-H, Agrawal A, Bandaru NK, Das SK, SailorMJ, et al. Computationally cuided photothermal tumor therapusing long-circulating gold nanorod antennas. Cancer Res. 2009;69:3892–9.
[47] Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Halas NJ. Nanoshell-mediated near-infrared thermal therapy of tumorsunder magnetic resonance guidance. Proc Natl Acad Sci. 2003; 100:13549–54.
[48] Gobin AM, Lee MH, Halas NJ, James WD. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 2007;7:1929–34.
[49] Duff DG, Baiker A. A new hydrosol of gold clusters. 1. Formation and particle size variation. Langmuir. 1993;9:2301–9.
[50] Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor specific nanoparticle delivery: effect of particle size. Cancer Res. 2000;60:4440–5.
[51] Link S, El-Sayed MA (1999) Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. J Phys Chem B 103:4212–4217
[52] Nikoobakht B, El-Sayed MA (2003) Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem Mater 15:1957–1962
[53] Gobin AM, O’Neal DP, Watkins DM, Halas NJ, Drezek RA, West JL. Near infrared laser-tissue welding using nanoshells as an exogenous absorber. LasersSurg Med. 2005;9999:1–7.
[54] O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. Photothermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett. 2004;209:171–6.
[55] Hashizume H, Baluk P, Morikawa S, McLean JW. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000;156:1363–80.
[56] Loo C, Lowery A, Halas NJ, West JL, Drezek R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 2005;5:709–11.
[57] Lowery AR, Gobin AM, Day ES, Halas NJ, West JL. Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomed. 2006;1:149–54.
[58] Lin AWH, Lewinski NA, West JL. Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells. J Biomed Opt. 2005;10:064035-1-10.
[59] Diagaradjane P, Shetty A, Wang JC, Elliott AM, Schwartz J, Shentu S, et al. Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an integrated antihypoxic and localized vascular disrupting targeting strategy. Nano Lett. 2008;8:1492–500.
[60] Liao H, Hafner JH (2005) Gold nanorod bioconjugates. Chem Mater 17:4636–4641
[61] Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, Katayama Y, Niidome Y (2006) PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release 114:343–347
[62] Maeda H (2001) The enhanced permeability and Retention (EPR) effect in tumor Vasculature: the key role of Tumorselective macromolecular drug targeting. Adv Enzyme Regul 41:189–207
[63] Maedaa H, Fanga J, Inutsukaa T, Kitamoto Y (2003) Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int Immunopharmacol 3:319–328
[64] Fang J, Sawa T, Maeda H (2003) Factors and mechanism of“EPR”effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv Exp Med Biol 519:29–49
[65] Paciotti GF, Myer L, Weinreich D, Goia D, Pavel N, McLaughlin RE, Tamarkin L (2004) Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv 11:169–183
[66] Greish K, Sawa T, Fang J, Akaike T, Maeda H (2004) SMAdoxorubicin, a new polymeric micellar drug for effective targeting to solid tumors. J Control Release 97:219–230
[67] McNeil SE (2005) Nanotechnology for the biologist. J Leukoc Biol 78:585–594
[68] Kommareddy S, Amiji M (2007) Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice. J Pharm Sci 96(2):397–407
[69] Pissuwan D, Valenzuela SM, Cortie MB (2006) Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends Biotech 24(2):62–67
[70] Sokolov K, Follen M, Aaron J, Pavlova I, Malpica A, Lotan R, Richards-Kortum R (2003) Real-time vital optical imaging of precancer using anti–epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Res 63:1999–2004
[71] Sokolov K, Aaron J, Hsu B, Nida D, Gillanwater A, Follen M, Macaulay C, Adler-Storthz K, Korgel B, Discour M, Pasqualini R, Arap W, Lam W, Richartz-Kortum R (2003) Optical systems for in vivo molecular imaging of cancer. Technol Cancer Res Treat 2(6):491–504
[72] Hayat MA (1989) Colloidal gold: principles, methods and applications, vol 1 edn. Academic, San Diego
[73] El-Sayed IH, Huang X, El-Sayed MA (2005) Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett 5:829–834
[74] Leamon CP, Low PS (2001) Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discov Today 6:44–51
[75] Nayak S, Lee H, Chmielewski J, Lyon LA (2004) Folatemediated cell targeting and cytotoxicity using thermoresponsive microgels. J Am Chem Soc 126:10258–10259
[76] Robins HI,Grosen E,Katschinski DM,et al.Whole body hyperthermia induction of soluble tumor necrosis factor receptor:implications for rtheumatoid disease[J].J Rheumatol,1999,26(12):2513-2516
[77] Dixit V, Bossche JV, Sherman DM, Thompson DH. Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjugate Chem. 2006;17:603–9.
[78] Xiaohua Huang,Prashant K. Jain,Ivan H. El-Sayed,Mostafa A.El-Sayed .Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers Med Sci (2008) 23:217–228
[79] Dixit V, Bossche JV, Sherman DM, Thompson DH. Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjugate Chem. 2006;17:603–9.
[80] Wang SN, Deng YH, Xu H, Wu HB, Qiu YK, Chen DW. Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin. Eur J Pharma Biopharma. 2006;62:32–8.
[81] Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998;351:417–8.
[82] Yang Y, Jiang J-S, Du B, Gan Z-F, Qian M, Zhang P. Preparation and properties of a novel drug delivery system with both magnetic and biomolecular targeting. J Mater Sci Mater Med. 2009;20:301–7.
[83] J. Perez-Juste, L. M. Liz-Marzan, S. Carnie, D. Y. C. Chan, P. Mulvaney,Adv. Funct. Mater. 2004, 14, 571– 579.
[84] F. Kim, J. H. Song, P. D. Yang, J. Am. Chem. Soc. 2002, 124, 14316–14317.
[85] C. J. Johnson, E. Dujardin, S. A. Davis, C. J. Murphy, S. Mann, J. Mater. Chem. 2002, 12, 1765–1770
[86] J. Perez-Juste, I. Pastoriza-Santos, L. M. Liz-Marzan, P. Mulvaney, Coord. Chem. Rev. 2005, 249, 1870–1901.
[87]潘碧峰,崔大祥,徐萍,李清,黄拓,陈浩.种子生长法制备长径比为2.5的金纳米棒.材料科学与工程学报,2007,25,(3).
[88]裴立宅.表面活性剂在合成金纳米晶溶胶中的应用[J].稀有金属快报,2004,23(11): 35-38.
[89] T Yonezawa,T Kunitake.Practical preparation of anionic mercaptoligand-tablized gold nanoparticles and their immobilization[J].Colloids Surf A, l999, l49(1-3): l93-l99.
[90] M K Kim,Y M Jeon,W S Jeon,et a1.Novel dendronstabilized gold nanoparticles with high stability and narrow size distribution[J].Chem Commun,200l,5(7):667- 668.
[91] Pham T, Jackson JB, Halas NJ, Lee TR. Preparation and characterization of gold nanoshells coated with self-assembled monolayers. Langmuir. 2002;18:4915–20.
[92] Wang YJ, Zhu SG, Xun CF. Biochemistry. 3rd ed. Beijing, China: Higher Education Press; 2003.
[93] Fuente JM, Berry CC, Riehle MO. Nanoparticle targeting at cells. Langmuir. 2006;22:3286–93.
[94] Chen JY, Saeki F, Wiley BJ. Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 2005;5:473–7.
[95]牛建丽.纳米金红外热疗诱导肿瘤细胞凋亡的研究.2009
[96] Shun-Ying Liu .Zhong-Shi Liang .Feng Gao.Shu-Fang Luo. Guo-Quan Lu. In vitro photothermal study of gold nanoshells functionalized with small targeting peptides to liver cancer cells. J Mater Sci: Mater Med DOI 10.1007/s10856-009-3895-x.
[97] Huiyu Liu, Dong Chen, Fangqiong Tang, Gangjun Du, Linlin Li, Xianwei Meng, Wei Liang, Yangde Zhang, Xu Teng and Yi Li.Photothermal therapy of Lewis lungcarcinoma in mice using gold nanoshellson carboxylated polystyrene spheres. Nanotechnology 19,(2008) ,455101 (7pp)