具良好体内清除效果的聚合物囊泡/Au纳米粒子热化疗体系

Polymer/Au particle thermochemotherapy system has been researched widely. However, small size Au particles have no hyperthermia functions. Although large size Au particles exhibit excellent hyperthermia properties, they suffer from being difficult to be cleaned out of the body; thus, it is challenging to achieve polymer/Au hybrid with both thermochemotherapy and excretion effects. To address this problem, the project will aim to encapsulate small size gold particles and chemotherapeutic drugs in biodegradable and pH sensitive polymer vesicles. The advantages of the this hybrid system are that small size Au particles aggregates located in vesicle have particular hyperthermia capacity, and polymers vesicle could encapsulate hydrophobic drug and hydrophilic drugs; thus, a drug vector with both thermochemotherapy capacity and good excretion effect could be constructed. Furthermore, polymer vesicle/Au particle hybrid will be able to disassembly due to the biodegradation of polymer in response to pH, thereby small size Au could be released from the vesicle, facilitating the excretion of polymer/Au particle hybrid cleaned out of the body. This project will provide a basis for balancing the biocompatibility of polymer vesicle/Au and its thermochemotherapy effect; a novel polymer/Au thermochemotherapy vector suited for clinical trial could be achieved.

聚合物/金粒子热化疗体系已被广泛研究，然而小尺寸金粒子不具备热吸收能力，具有热吸收效果的大尺寸金粒子又存在体内清除困难的问题，因此，难以获得具有热疗效果又易被体内清除的聚合物/金粒子热化疗体系。针对上述问题，本课题拟设计具有pH响应性、可生物降解的聚合物并包载小尺寸金粒子和化药，此体系的优势在于：聚合物自组装形成囊泡使体系中小尺寸金粒子聚集体产生独特的热效应，与化疗药物共同作用赋予聚合物/小尺寸金粒子杂化体系热化疗的功能；此外，pH敏感的以及可生物降解聚合物囊泡在酸性环境中解组装，释放出小尺寸金粒子，从而克服聚合物/金粒子体系难以被体内清除的问题。本项目将为平衡热化疗用聚合物/金粒子的生物相容性与热化疗效果研究提供基础数据，并进一步为实现热化疗用聚合物/金粒子的临床前研究提供重要的载体材料。

本项目用两亲高分子聚合物接枝尺寸约6nm金粒子后，位于囊泡膜中金粒子间距离减小，金粒子间致密连接，SPR峰位移至近红外区域。随着疏水聚合物组分比例增加，组装体发生胶束到复合胶束的结构转变，热疗效果逐渐增强。，本项目制备通过系列高分子接枝6nm金粒子技术，构建了兼具体内热疗效果以及体内代谢安全性的热疗体系。 同时利用两个高分子胶束结构包裹疏水性的抗癌药物，从而具有光热疗-化疗联合治疗的效果。同时，上述金粒子组装体具有良好的这的CT成像及光声成像效果，构建了生物安全性更高的热化疗多功能诊疗的体系。