肿瘤微环境响应性脂质体的构建与肿瘤药物深度递送研究

项目名称： 肿瘤微环境响应性脂质体的构建与肿瘤药物深度递送研究

项目编号： No.31500807

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 刘雅

作者单位： 中国海洋大学

项目金额： 21万元

中文摘要： 癌症治疗是人类面临的重大健康难题之一，设计与制备新型高效、低毒、肿瘤微环境响应性的纳米药物载体成为癌症治疗的研究热点。然而大多数纳米载体穿透肿瘤组织的能力差，难以将药物递送到肿瘤实质。本项目拟构筑响应性多肽网状修饰的脂质体，在脂质体上修饰肿瘤靶向穿透性多肽（iRGD），并包载化疗药物，使其同时具有良好的生理环境稳定性及高效的抗癌效果。考察响应性网状修饰脂质体对基质金属蛋白酶（MMPs）的特异性响应及其药物可控释放的动力学，总结纳米颗粒理化参数与响应性之间的关系；检测响应性网状修饰脂质体的肿瘤组织靶向穿透性药物递送的效果，阐明iRGD肽介导的药物肿瘤深度递送的作用机理；研究响应性网状修饰脂质体的体内分布、药效和安全性，对抑制体内实体肿瘤的生长效果进行探讨。通过本项目的实施，旨在为肿瘤微环境响应性纳米材料的设计及加速纳米药物的肿瘤靶向穿透性递送提供新思路，拟推动纳米技术在生物医学领域的发展。

中文关键词： 肿瘤微环境；响应性；脂质体；肿瘤穿透性；药物递送

英文摘要： Cancer therapy is one of the important human health problems. Considerable efforts has been devoted to design and prepare highly-efficient, low toxic and tumor microenvironment responsive nanocarriers for drug delivery. However, most nanocarriers exhibit poor ability of penetration into tumor tissues and difficult to deliver drugs to the tumor parenchyma. In this proposal, we plan to construct polymeric peptides weaved nanovesicles (PP-W-NVs) with iRGD as a target ligand to achieve high physicochemical stability and enhanced cancer therapy effect. The responsiveness of PP-W-NVs toward matrix metalloproteinases (MMPs) and the dynamics of drug controlled release will be studied systemically to project the relationship between structural/functional parameters and responsive kinetics. Investigating the tumor targeted penetration of PP-W-NVs to demonstrate the mechanisms of iRGD mediated drug delivery. Finally, the biodistribution, biosafety issues and antitumoral efficacy will be investigated by using xenogragted mice as models. Altogether, this research proposal aims to develope novel strategies for preparation of tumor microenvironment responsive nanomaterials and facilitation of tumor targeted penetration drug delivery in vivo for synergestic cancer therapeutics. The successful demonstration of this strategy will open new avenue for nanotechnology and biomedicine in the future.

英文关键词： Tumor Microenvironment;Responsive;Nanovesicle;Tumor-Penetrating ;Drug Delivery