如何提高分子抗肿瘤纳米药物的治疗效果是急待解决的问题。纳米药物在体内的命运与其表面特性紧密相关。本项目基于前期研究基础，拟围绕“如何调控高分子纳米药物的表面特性调控其在体内的命运，从而提高肿瘤治疗效果”的关键科学问题，通过合成不同化学特性的聚磷酸酯，构建单一特性可精准调控的纳米药物载体；重点研究纳米特性如何影响纳米在体内的循环、肿瘤富集与清除、血管与组织渗透、组织内肿瘤细胞与基质细胞摄取等的联系；同时将纳米特性、体内命运与蛋白吸附等体外模型实验、肿瘤微环境与病理学特症等分析对应，结合计算等探讨其中的机制与原理；进一步优选纳米药物递送体系，进而优选纳米药物递送体系，实现高效抗肿瘤治疗；并同时反馈纳米载体的设计与构建。本项目作为纳米药物体内命运的基础研究，将为载体设计和应用提供理论支持和指导。

How to improve the therapeutic effect anti-cancer polymeric nanomedicine has been a critical issue in the area of cancer therapy. The in vivo fate of nanomedicine has been proven to be closely related to its surface properties. Based on our previous research, we propose to study “how to control the in vivo fate of nanomedicine by regalating their surface properties and thereby to improve the ultimate anti-cancer therapeutic effect. We will synthesize various polyphosphoesters with different chemical properties and prepare nanocarriers with precisely tunable surface properties. We will investigate how surface properties of nanomedicine affect its in vivo blood circulation, tumor accumulation and clearance, extravasation and tumor penetrations, as well as the internalization by tumor and stromal cells. The relationship between their in vivo fate, surface properties, and protein adsorption will be studied by both in vitro models and theoretical calculations. The tumor microenvironment and pathological analysis will also be performed and correlated to in vivo experiments results. Finally, we will evaluate the in vivo anti-cancer therapeutic effect of these nanomedicines in various tumor models, whose results can be further used to guide the design and construction of nanomedicines. The project as a basic study of nanomedicine will provide theoretical support and guidance for anti-cancer nanomedicine design and application.