聚合物与上转换纳米粒子复合物组装体的构筑及其程序化光激活疗法研究

近年来基于可将近红外光转化为紫外或可见光的上转换纳米粒子平台在光动力治疗领域取得了长足的进步和发展，但在实施光动力治疗过程中，以下两方面因素都会降低其治疗效果：1)细胞对颗粒的外排作用会降低颗粒的利用率；2)细胞清除光动力治疗产生效果所需自由基的固有能力。基于此，本项目拟利用嵌段聚合物诱导具有正交光发射属性的上转化纳米粒子进行囊泡组装体的构筑，并在组装体进入细胞后的不同阶段施以程序化光激活，用以帮助颗粒逃逸内吞小体至细胞质以提高颗粒的利用率；敲除负责破坏自由基的基因用以抑制自由基的清除，在此基础上再实施光动力治疗，以达到提高其治疗效果的目的。该研究有助于推动有机聚合物，无机上转换粒子以及生物医学等学科的交叉及发展，也为其他需要程序化光激活的领域提供新的思路和方法。

Near infrared (NIR) light-excitable upconversion nanoparticle （UCNPs）based nanoplatform has been shown successfully in photodynamic therapy （PDT）, as they can act as a nanotransducer to absorb NIR and convert it to UV/visible light. UCNPs have been used for PDT with relative success but their effectiveness as a standalone treatment is low. Primary reasons for the lower efficiency of PDT could be due to the recycling of the nanoparticles by the cellular machinery and the inherent ability of the cells to withstand and combat free radicals. The goal of this proposal is to utilize block polymers to induce UCNPs with orthogonal emissive emission self-assemble into vesicles and applied it into programmable photoactivation at different stages after the assembly enter into the cells in order to help the particles escape from endosome into the cytoplasm to improve the utilization of particles; knock down the genes that responsible for destroying free radicals, and then PDT was performed to obtain better cell killing efficiency. This research is not only helpful to promote the development of organic polymers, inorganic UCNPs and biomedical science, but also provide some new thoughts and methods for other fields that require programmed photoactivation.