肿瘤微环境调节及响应性多功能嵌段聚合物纳米载体的构筑

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• 英文论文题名：Multifunctional Polymeric Nanocarriers with Regulation and Response to Tumoral Microenvironments
• 论文作者：李军杰 ; 葛治伸
• 英文论文作者：Junjie Li ; Zhishen Ge ; CAS Key Laboratory of Soft Matter Chemistry ; Department of Polymer Science and Engineering ; University of Science and Technology of China
• 年：2016
• 作者机构：中国科学技术大学高分子科学与工程系中科院软物质化学重点实验室;
• 论文关键词：药物输送 ; 环境响应性 ; 聚合物前药 ; 囊泡 ; 胶束
• 会议召开时间：2016-07-01
• 会议录名称：中国化学会第30届学术年会摘要集-第三十八分会：纳米生物效应与纳米药物化学
• 语种：中文
• 分类号：TB383.1;TQ460.1
• 学会代码：ZGHY
• 会议名称：中国化学会第30届学术年会-第三十八分会 ; 纳米生物效应与纳米药物化学
• 会议地点：中国辽宁大连
• 主办单位：中国化学会
• 学会名称：中国化学会
• 页数：1
• 文件大小：151k
• 原文格式：D
• 会议级别：全国

摘要

在高分子纳米载体领域,基于肿瘤独特的微环境刺激信号,发展新型的高效响应性可控释放载体体系,代表了新一代高分子纳米载体的发展方向。肿瘤组织细胞外微环境相对于正常组织存在信号特异性明显,响应性高分子可在组织层面响应等诸多优势,但信号差异较小,为响应性高分子应用带来困难~([1])。为了能够实现载体在病变组织层面的响应性,我们设计并制备了兼具调节肿瘤微环境特征并对肿瘤微环境响应的多功能纳米载体体系。首先,发展了含Vc基团的抗坏血酸棕榈酸酯(PA)负载于两亲性嵌段聚合物PEG-b-PCPTOEMA(PCPTOEMA为聚合的草酸酯键连接喜树碱和羟乙基甲基丙烯酸酯单体)纳米胶束,发现该纳米载体在细胞培养基中以及肿瘤组织中都可以将H_2O_2浓度调高至草酸酯键发生断裂所需的浓度,从而实现基于H_2O_2和喜树碱的联合氧化-化疗~([2])。其次,构筑了外壳层为聚乙二醇(PEG),内壳层为穿膜分子的基质金属蛋白酶(MMP)响应性嵌段聚合物非对称囊泡,同时负载亲水性MMP抑制剂和疏水性药物,在肿瘤组织MMP作用下,释放MMP抑制剂,同时转变为球形粒子,穿膜分子翻转至粒子表面,促进更加高效的负载疏水药物粒子进入细胞。
In the field of polymeric nanomedicine, construction of systems with high-efficiency drug-loading and on-demand drug release represents the new trend. As compared with normal tissues, tumor tissue microenvironment shows distinctive features. However, the differences between them are very subtle hampering the in vivo applications of stimuli-responsive polymers as drug nanocarriers. We designed and constructed multifunctional nanocarriers with simultaneous regulation and response to tumoral microenvironments. First, palmitoyl ascorbate(PA) as a prooxidant for hydrogen peroxide(H_2O_2) production in tumor tissue is strategically compiled into a H_2O_2-responsive camptothecin(CPT) polymer prodrug micelle, which achieved synergistic oxidation-chemotherapy. Second, the matrix metallo proteinases(MMP)-responsive asymmetric vesicles with PEG as outer corona and cell-penetrating molecules as inner shells were used to simultaneously encapsulate hydrophilic MMP inhibitor and hydrophobic drugs, which achieved MMP-responsive morphological transition with cell-penetrating molecules moving to the particle surface, MMP inhibitor release, and promoted cellular internalization.

引文

[1]Ge,Z.S.;Liu,S.Y.Chem.Soc.Rew.2013,42:7289.
    [2]Li,J.J.;Ke,W.D.;Wang,L.;Zhang,P.;Chen,Q.X.;Ge,Z.S.J.Control.Release 2016,225:64.