近红外光控药物顺序释放体系的构建及高效能量传递机制研究

The application of photo-controlled drug sequential release systems have been a highly effective way to surmount multidrug resistance of cancer cells. However, it is difficult to enable them to release drugs in deep cancerous tissues due to the limited penetration depth of the excitation wavelength, which greatly hinders their practical applications. In this project, a new type of near-infrared light-controlled drug sequential release system will be constructed by utilizing rare-earth-doped upconversion nanoparticles as the core, the mesoporous silica as the intermediate layer and a self-assembled polyelectrolyte multilayer containing a green-light-sensitive polymer as the shell. Firstly, by studying the relationship between the processes of energy transfer of rare earth ions and high-order energy level population, illuminates that high-order multi-photon processes depend on the composition, structure, and size, etc., then reveals the upconversion luminescence enhancement mechanism of the prepared luminescent materials. Secondly, by studying the photophysical and photochemical properties of the green-light-sensitive monomers, methyl boron-dipyrromethene derivatives, before and after polymerization, illuminates that its photocleavage efficiency depends on the structure of the polymer, then realizes the preparation of the green-light-sensitive polymer with a high quantum yield of photoreaction. Finally, the effects of energy transfer between upconversion nanoparticles and green-light-sensitive polymers on the release of drug will be investigated, reveals the mechanism of efficient energy transfer between upconversion nanoparticles and polymers. Our goal of this project is to construct a smart near-infrared light-controlled drug release nanocarrier with efficient energy transfer and provide some useful experimental basis. It is valuable in academic research.

光控药物顺序释放体系是解决癌细胞耐药性的重要途径之一，但其难以在深部癌变组织被激发而释放药物，严重阻碍其实际应用。本项目拟构建一种稀土掺杂上转换纳米粒子为核，介孔硅为中间层，绿光响应自组装聚电解质薄膜为壳的近红外光控药物顺序释放体系。首先，研究稀土离子之间能量传递过程对上转换纳米粒子高阶能级布居的影响，阐明高阶上转换过程对材料组成、结构、尺寸等的依赖关系，揭示材料尺寸对上转换发光的增强机制，制备高效发光的上转换纳米粒子。其次，研究具有甲基氟化硼二吡咯结构的绿光响应单体在聚合前后光物理、光化学性质的变化，揭示高分子结构对绿光切断效率的影响规律，制备出具有高光化学反应量子产率的绿光响应高分子。最后，研究上转换纳米粒子与绿光响应高分子之间能量传递对药物释放效率的影响，揭示上转换纳米粒子与高分子间高效能量传递的机制，为构建高效能量传递的近红外光控智能药物载体提供实验依据，具有一定学术价值。

顺序释药载体具有逐步释放多种药物的功能，可有效避免癌细胞耐药性的产生，从而提升治疗效果。光控顺序释药载体由于其较高的“普适性”而备受关注，即不依赖特定化学环境释放药物。然而，它们几乎都采用紫外光和可见光作为激发光源，但这些光源对生物组织的穿透能力低，导致载体在深部癌变组织中难以激发并释放药物。针对这些问题，本项目集成了稀土上转换发光纳米粒子、介孔硅和可见光响应有机材料，旨在构建一类可在深部癌变组织中激发并顺序释放药物的近红外光控纳米载体。主要取得以下研究成果：揭示了上转换发光纳米粒子的组成设计和尺寸效应对其发光行为的影响规律，阐明了获取高效上转换发光的机制，并制得了近红外光照下高效发射绿光和蓝光的系列上转换发光纳米粒子；实现了光响应分子的模块化合成，突破了传统合成路线复杂、响应波长难以调控的难题，揭示了绿光响应高分子结构和性能之间的关系，并获得了具有高光化学反应量子产率的绿光响应高分子；构建了近红外光控药物顺序释放纳米载体，探究了上转换发光材料及光响应高分子结构对药物顺序释放的影响规律，并实现了药物的高效释放。以上研究成果为构建高效能量传递的近红外光控智能药物载体提供了实验依据。另外，本项目光响应材料和纳米载体的构建方法具有普适性，可供相关研究领域参考。值得指出的是，从玉米芯等废弃生物质资源获取的糠醛，是合成本项目光响应材料的重要起始原料，我们的研究证实了糠醛基光敏材料不仅可用于生物医用材料领域，还可用于隐形防伪和食品安全预警，有望实现废弃生物质资源的高值利用。