基于透明质酸的智能纳米载体构建及其靶向抗肿瘤研究

项目名称： 基于透明质酸的智能纳米载体构建及其靶向抗肿瘤研究

项目编号： No.51303003

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 一般工业技术

项目作者： 林英

作者单位： 安徽工程大学

项目金额： 25万元

中文摘要： 发展兼具肿瘤靶向功能和癌细胞内环境敏感的高分子药物载体，显著提高肿瘤部位给药准确性的同时实现药物癌细胞内暴释，可以急剧提升药效，是当前化疗医学发展的主要趋势。本项目拟选用有肿瘤靶向能力的透明质酸同胱氨酸衍生物，在静电驱动协同下聚合交联合成携带大量二硫键的纳米微球，对癌细胞内还原性环境敏感的二硫键将使载药微球选择性释放大量药物在癌细胞内。为延长微球体内循环时间的同时增加其瘤内渗透深度，深入研究合成影响因素以可控合成单分散的且尺寸适当的微球。本项目首次在合成纳米微球中不消耗透明质酸用作靶向位点的羧基，并将靶向功能与还原敏感性整合在一个微球上，有望实现药物对肿瘤的靶向传输和定点释放，达到准确治疗肿瘤的目标。

中文关键词： 透明质酸；靶向；药物传输；成像；纳米微球

英文摘要： Polymeric drug delivery systems with tumor-targeting ability and stimuli-sensitivity to intracellular environment can significantly improve the accuracy of drug delivery, realize drug burst release in the cancer cells, and thus sharply improve antitumor effect, which is one of the major topics in current medicine of chemotherapy. In this project, we aim to synthesize the nanospheres bearing abundant disulfide through the assembly of hyaluronic acid (HA) with tumor targeting and a derivative of cystine driven jointly by electrostatic interaction and polymerization, and large amounts of drugs would be selective released in cancer cells from the nanospheres since disulfide bonds are prone to rapid cleavage under the reductive environment inside cells. Monodisperse nanospheres with appropriate size will be controllably synthesized by in-depth studying its impact factors, which is expected to not only prolong the blood circulation time of the nanospheres for in vivo applications, but also improve the penetration depth within tumor. Compared with related reported in literature, carboxyl groups of HA acting as recongnition sites for HA receptors will not be consumed in this nanospheres for the first time. By integration of targeting capability and reduction-sensitivity, the developed multifunctional nanospheres are exp

英文关键词： hyaluronic acid；targeting；drug delivery；imaging；nanosphere