近红外二区响应性高分子纳米复合材料的构建及其性能研究

近红外二区荧光染料（NIR-Ⅱ，1000~1700 nm）由于发射波长较长，在生物成像中具有更高的时空分辨率和更深的组织成像深度。目前，NIR-Ⅱ主要有无机材料、共轭聚合物和有机小分子。但它们一般存在着水溶性、可降解性、生物相容性差等缺点，限制了其在生物体中的应用。本项目拟开发一种水溶性良好并生物可降解的红外二区高分子，进一步包裹筛选出的具有最佳免疫源性细胞死亡（ICD）效应的四价铂，形成可发红外二区荧光的纳米复合物，其特点是：1）可跟踪材料在体内的代谢、分布；2）可通过红外二区激光照射，激活肿瘤部位氧气，产生单线态氧（ROS），导致癌细胞凋亡，诱导肿瘤产生ICD效应（依赖氧气）；3）光照产生的 ROS使高分子降解，释放铂药。铂药可随后导致细胞凋亡和诱导ICD效应（不依赖氧气）。因此纳米复合物通过双重ICD效应，使耐铂型卵巢癌从“冷肿瘤”变成 “热肿瘤”，最终实现化疗和免疫治疗的协同治疗。

NIR-II region fluorescence (NIR-II, 1000-1700 nm) shows higher spatial-temporal resolution and deeper tissue imaging depth in biological imaging due to its long emission wavelength. At present, NIR-Ⅱ materials mainly includes inorganic materials, conjugated polymers and organic small molecules. However, they generally have the disadvantages of limited water solubility, biodegradability and poor biocompatibility, which limits their application in body. This project plans to develop a kind of NIR-II polymer with good water solubility and biodegradability, and further it was used to package the screened platinum(IV) prodrugs with the best effect of immune genic cell death (ICD) effect to form a nanocomposite with NIR-II fluorescence. It has the following characteristics: 1) it can track the metabolism and distribution of nano-materials in the body; 2) it can activate the oxygen in the tumor site and produce singlet oxygen (ROS) under NIR-II light irradiation, which can result in cancer cell apoptosis and induce ICD effect (oxygen dependent); 3) the ROS produced by light irradiation can help the polymer degrade and platinum drugs are then released. Platinum drugs can subsequently induce apoptosis and ICD effects (oxygen independent). Therefore, the nanocomposites can turn platinum resistant ovarian cancer from "cold tumor" to "hot tumor" through dual ICD effect, and finally achieve the synergistic treatment via chemotherapy combined with the immunotherapy.