协同响应激活的高特异性肿瘤诊疗系统

肿瘤特殊的微环境为肿瘤特异性诊疗提供了新的思路和可能。但已有响应单一微环境的诊疗方法仍不理想，因为其他部位也可能具有肿瘤的某种微环境特性，导致非特异性响应；而同时具有两种肿瘤微环境特性的部位则非常少。基于此，本项目提出一种全新的策略，构建协同响应激活的高特异性肿瘤诊疗系统。在四嗪（Tz）衍生的无信号荧光前体和反式环辛烯（TCO）衍生的无活性前药合成基础上，将荧光前体和TCO衍生小分子（或者是前药和Tz衍生小分子）分别装载入不同的肿瘤微环境敏感纳米颗粒中。通过两种肿瘤微环境特性以及Tz与TCO之间逆电子效应Diels-Alder反应的协同作用，使得仅在肿瘤组织定点激活荧光信号或药效，实现高特异性的肿瘤荧光成像诊断或治疗。进而，将更多具有不同响应特性的纳米颗粒与荧光前体/前药以及TCO/Tz组合，形成多种可选的方案，提供一个普适性的肿瘤高特异性诊疗平台，促进肿瘤诊疗研究的发展。

A new idea and possibility for tumor diagnosis and treatment is provided by the specific tumor micro-environment. However, the effects of reported methods in response to one of the characters of tumor micro-environment are not satisfactory due to the nonspecific response in other parts of the body. In this project, a new strategy is proposed, in which, Tz derivated pre-fluorescer or TCO derivated prodrug will be synthetized and loaded to the tumor micro-environment sensitive nanoparticles, and TCO or Tz will be loaded to another kind of nanoparticles. Then highly specific tumor imaging or treatment is expected by cooperating the activation effect of two different micro-environment characters with iEDDA. Furthermore, different tumor micro-environment sensitive and loaded nanoparticles will be prepared to provide a universal platform. This work is hopefully to promote the development of tumor diagnosis and treatment study.