基于K5多糖可逃避免疫清除的仿生靶向药物传递系统研究

This work aims to construct a bioinspired nano drug delivery system (DDS) based on K5 polysaccharide, which can confer resistance to host immune clearance by being recognized as endogenous material, for targeting delivery and controlled releasing of hydrophobic anti-cancer drugs. This DDS will be able to avoid the contact between drug and immune cells by escaping from immune phagocytosis and clearance, and thus to promote bioavailability of drugs and decrease the side-effects to immune system. To achieve this goal, the majority of this work are designed as following: 1) Building stable core-shell structural nanocarriers through regulating the hydrophilicity of K5 polysaccharide derivant and its self-assembly behavior. 2) Introducing ligands to improve the non-specific tumor targeting drug delivery ability. 3) Conjugating carrier and drug molecules through a stimuli-response functional linker for in vitro/vivo controlled release in tumor micro-milieu. 4) Tracking and evaluating the nano-vehicle in evading immune phagocytosis and clearance by fluorescence imaging technology.

利用K5多糖可被宿主免疫系统识别为内源性物质，可逃避免疫清除的特点，构建仿生纳米药物传递系统，包载疏水性抗癌药物。一方面逃避免疫吞噬及清除，提高药物的生物利用度；另一方面避免药物与免疫细胞接触，降低化疗药对免疫机能的毒副作用。研究主要包括以下几方面内容：调控材料亲疏水比及自组装行为，制备具有稳定核-壳结构的纳米药物载体；研究靶向配体的引入对体系药物靶向传递性能的影响；具有刺激-响应功能链接的引入对药物在体外/体内控制释放的作用；进一步利用荧光成像技术，跟踪评价载体在逃避免疫细胞吞噬清除方面的效果。探讨仿生药物传递系统在提高药物生物利用度及降低化疗毒副作用方面的关系。