嵌段共聚物包覆的BiVO4纳米复合超粒子的构筑及肿瘤诊疗的研究

BiVO4 nanoparticles (NPs) have been considered as the idea photosensitizer for photodynamic therapy (PDT) due to their excellent photocatalytic activity, low toxicity, and abundant resources. Furthermore, Bi is a high atomic number element, which possesses high K-edge value and good X-ray attenuation properties. Thus, BiVO4 NPs have the potential to be used as the safe contrast agent for CT imaging. In this project, we hope to develop a simple colloidal synthesis strategy to prepare BiVO4 NPs with size in nanoscale, good dispersibility, controllable morphologies and exposed crystal faces. Then we fabricate amphiphilic-block-copolymers capped BiVO4 superparticles (SPs) following the emulsification method by employing BiVO4 NPs as the building blocks, amphiphilic-block-copolymers as the surfactants for cancer CT imaging and PDT. Our researches will focus on the following aspects: first, investigating the effects of experimental parameters on the sizes, morphologies, and exposed crystal faces of the BiVO4 NPs; second, studying the relationship between the exposed crystal faces of BiVO4 NPs and the species of their photogenerated ROS; third, discussing the effect of the coupling interactions between neighboring BiVO4 NPs on their theranostic properties; finally, disclosing the functions of various ROS on the inhibition of tumor growth.

BiVO4纳米粒子由于具有优异的光催化活性、绿色无毒、储量丰富等优点，被视为理想的光敏剂用于光动力治疗。同时，由于Bi元素具有较高的原子序数和X射线吸收系数，因此BiVO4纳米粒子也可用于CT成像的造影剂。本项目拟开发简便的胶体合成路线用于制备尺寸小、分散性好、形貌（暴露晶面）可控的BiVO4纳米粒子，然后以这些BiVO4纳米粒子作为结构基元，以生物可降解的双亲嵌段共聚物作为表面活性剂，利用微乳液模板技术制备纳米复合超粒子，并将其应用于恶性肿瘤的CT成像和光动力治疗。研究主要包括以下几个部分：（1）合成条件对于BiVO4纳米粒子的尺寸、形貌、及暴露晶面的影响；（2）建立BiVO4纳米粒子暴露晶面与其光生ROS种类和强度之间的联系；（3）探讨集合效应对于BiVO4纳米粒子光动力治疗性能及CT成像性能的促进作用；（4）揭示不同种类ROS对于恶性肿瘤细胞及组织的抑制作用机制。

恶性肿瘤是威胁人类健康的第一杀手。利用放疗这一单一治疗手段很难彻底清除肿瘤组织并遏制其转移。本项目依托胶体合成方法和自组装技术构筑了一系列具有多模式诊疗功能的含Bi纳米材料，并将制备技术拓展至其他材料体系，取得了一系列重要成果：（1）通过深入揭示纳米材料的结构、组成与其性能之间的构效关系，设计开发在高能射线激发下电荷分离效率高的Bi基纳米材料，并借助聚合物作为载体构筑放疗增敏性能优异、生物兼容性好的纳米复合放疗增敏剂，大幅提升放疗治疗效果；（2）优选聚合物纳米载体以及负载物的种类与功能，充分利用共价键及非共价超分子相互作用，设计构筑基于放疗的多功能纳米复合诊疗平台，实现对恶性肿瘤的多模式成像与多种治疗手段的协同治疗。在本项目资助下，共发表SCI论文10篇，获授权中国发明专利2项，培养硕士研究生4人。