物理化学性质和肿瘤种类对高分子纳米粒子在小鼠体内代谢和分布的影响研究

抗肿瘤药物高分子纳米制剂是新型化疗药物的重要研究方向，高分子纳米载体可提高抗肿瘤药物的靶向能力和抗肿瘤效果，这其中重要原因之一是纳米载体可以改善原有抗肿瘤药物的体内代谢和生物分布行为，使药物在肿瘤部位相对富集，降低毒副作用并提高疗效。纳米粒子的物理化学性质以及肿瘤种类是抗肿瘤药物高分子纳米粒子的代谢动力学和生物分布的重要影响因素，寻找它们之间的一般规律，是一项重要的基础研究工作。本项目拟以光声成像为技术手段，以近红外染料标记的聚乙二醇化聚乳酸或者聚谷氨酸高分子纳米粒子为研究对象，实时定量跟踪高分子纳米粒子在荷瘤小鼠体内各组织和器官的浓度变化，系统研究粒径、聚乙二醇分子量、聚乙二醇接枝密度、载药量、表面电荷、肿瘤靶向基团种类和含量、肿瘤种类对高分子纳米粒子的体内代谢和生物分布的影响，总结一般规律，为新型肿瘤靶向高分子纳米载体的设计提供指导和参考。

Polymeric nanoparticle formulation of anticancer drug is an important research direction of chemotherapy drugs. Polymer nanocarrier can improve the tumor targeting of the anticancer drugs and anti-tumor effect because nanocarrier can better the pharmacokinetics and biodistribution of the original drug. The loaded drug is relatively enriched at the tumor site, which leads to the reduction of side effects and the improvement of efficacy. The physical and chemical properties of nanoparticles and tumor type have great influence on the pharmacokinetics and biodistribution of polymeric nanoparticles. Search for the general laws is an important fundamental research field. This project intends to track quantitatively the real-time concentration changes of near-infrared dye-labeled pegylated polylactic acid or polyglutamic acid nanoparticles in tissue and organ of tumor-bearing mice. It is expected that the general laws of particle size, molecular weight of polyethylene glycol, graft density of polyethylene glycol, drug loading content, surface charge, the type and content of tumor targeting ligands, tumor type affecting the pharmacokinetics and biodistribution of polymer nanoparticles are figured out. These may be used as guidance and reference for the design of new tumor targeting polymer nanocarriers.