高性能纳米恒温光热体系的构筑及在耐药菌体内感染精准治疗中的应用

抗生素的大量以及不合理使用导致细菌耐药性的产生，对人类健康造成了严重危害。近年来，光热治疗已经发展成为耐药菌感染的有效治疗手段，然而大多数光热治疗体系不具备内在控温机制，因而在光热治疗过程中对组织造成过热损伤。本项目围绕“功能基元+序构”这一设计理念，设计合成具有近红外响应的螺内酯类染料，通过与质子显色剂及天然来源相转变材料复合组成“功能基元”，利用体系的物态变化特性实现“功能基元序构”的可逆调控，构筑具有内在控温机制的恒温光热体系，系统性研究恒温维持过程的详细机理；发展纳米分散与表面聚合相结合的“自上而下”的制备方法，实现恒温光热体系的纳米化转变，探究纳米恒温光热材料与耐药菌间的体外相互作用；利用耐药菌感染的动物模型，系统性比较恒温热疗与非恒温热疗在组织损伤以及治疗效果上的差异。该项目的实施将有助于发展“功能基元序构”高性能生物医用材料，为耐药菌体内感染的精准治疗提供材料与技术支撑。

The over- and misuse of antibiotics lead to the emergence of bacterial resistance, which poses serious threat to human health. In recent years, photothermal therapy has developed into an effective strategy to fight against drug-resistant bacteria. However, most photothermal systems do not possess a built-in temperature-control mechanism, resulting in overheating damages to normal tissues during photothermal therapy. Focusing on the paradigm of “functional unit + ordered structure”, we plan to design and synthesize near-infrared responsive spironolactone-type dyes, which are then combined with proton-donating developers and naturally-occurring phase change materials to form the “functional unit”. By means of the physical state changes of the composite materials, it is possible to achieve the reversible regulation of “the ordered structure of the functional unit”. We will build thermostatic photothermal systems with a built-in temperature-control mechanism and systematically study the detailed mechanism of the thermostatic process. We will develop a “top-down” technique that combines nanodispersion and in situ surface polymerization to achieve the nanoformulation of the thermostatic photothermal systems. We will explore the in vitro interactions between the thermostatic nanoparticles and drug-resistant bacteria. By establishing animal models with drug-resistant bacterial infections, we will systematically compare the differences between non-thermostatic and thermostatic photothermal systems in terms of tissue damages and therapeutic outcomes. The implementation of this project will boost the development of high-performance biomedical materials that are inspired by the paradigm of “functional unit + ordered structure” and provide essential material and technical supports for the precise treatment of drug-resistant bacterial infections.