pH敏感型靶向纳米载体/吡啶类双光子化合物在光动力治疗癌症方面的应用探索

项目名称： pH敏感型靶向纳米载体/吡啶类双光子化合物在光动力治疗癌症方面的应用探索

项目编号： No.81503009

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 罗雷

作者单位： 西南大学

项目金额： 17.9万元

中文摘要： 光动力疗法（PDT）是近期发展的利用光和光敏剂（Ps）高效治疗肿瘤疾病的新型疗法之一。但Ps在体内分布的主动靶向性差、难溶于水以及受限于穿透力较弱的较短波长光源激发（600-700nm），仅能治疗皮肤和浅表肿瘤，是该领域亟待解决的科学问题。本项目依据原子转移自由基聚合原理合成pH敏感型两嵌段共聚物并修饰靶向性cRGD环肽，同时装载新型吡啶类双光子化合物（L2pa）和Ps，以构建纳米给药系统，靶向肿瘤组织，释出装载物，采用1000nm左右穿透力较强的近红外光源激发富集在肿瘤内的L2pa，通过荧光共振能量转移效应间接激发Ps产生单线态氧，杀伤肿瘤细胞和新生微血管，实现双光子光动力疗法对深部肿瘤及大块肿瘤的pH、cRGD和激发光三重靶向治疗。系统研究单线态氧产生、细胞摄取、细胞毒性、靶向性、药效学和药动力学等，旨在发展PDT理论，拓宽Ps治疗范围并提高疗效，为肿瘤疾病的治疗提供新思路和新方法。

中文关键词： pH敏感型；纳米给药系统；双光子吸收；光动力疗法；肿瘤靶向

英文摘要： Photodynamic therapy (PDT) is one of the new approaches for cancer therapy. However, the applications of most photosensitizers (Ps) are restricted on skin and superficial tumor on account of their poor active targeting ability while distributing in the body, poor water solubility and excitement by light with a comparatively short wavelength (600-700nm), which leads to poor penetration. Therefore, this project is designed to overcome these shortages. A tumor targeting cRGD decorated pH sensitive diblock polymer is employed as nano delivery system to co-encapsulate pyridine two-photon compound (L2pa) and Ps, which is synthesized based on the Atom Transfer Radical Polymerization (ATRP) theory and designed to target tumor cells and release fast. And then, near infrared light with an approximately 1000nm wavelength is able to indirectly excite Ps through fluorescence resonance energy transfer which can upconvert the energy of near infrared light to Ps molecules. Tumor cells and neovascular in tumor tissue are damaged by the generated singlet oxygen. Therefore, this delivery system is supposed to treat deeper tumors through the application of ‘triple targeting’ (pH, cRGD and light) two-photon PDT. Generation of singlet oxygen, cellular uptake, cell toxicity, targeting ability, pharmacodynamics and pharmacokinetics are studied in this project. According to this project, the theory of PDT is expected to be developed and the new approach of cancer therapy to be provided. Furthermore, efforts are being made to expand the application of current Ps.

英文关键词： pH sensetive;Nano drug delivery system;Two photon absorption;Photodynamic thearpy;Tumor targeting