基于离子液体的智能纳米诊疗剂构建及肿瘤热疗作用机制探索

Tumor imaging guided microwave thermotherapy as well as real-time monitoring of therapeutic effect has attracted enormous attention in the biological analysis and medicine area. However, the performance of current microwave thermotherapy sensitizers is restricted to microwave induced heating. Many difficulties still exist in the controlled assembly of imaging contrast agents and microwave thermotherapy sensitizers. In order to solve those problems, this project aims to design functionalized ionic liquids based on anti-tumor drugs or active pharmaceutical ingredients for improving the efficacy of microwave thermotherapy. Then ionic liquids will be loaded in imaging probe modified hollow silica nanoparticles, which are further decorated with acid-sensitive polyethylene glycol conjugates. This theranostic nano-agent is expected to accumulate and activate in tumor acidic environment as well as exhibit the function of each component. By thoroughly exploring the potential applications of ionic liquid-loaded hollow silica materials in the imaging and microwave thermotherapy of tumor, it would provide the theoretical support and innovative concept for the design of efficient multifunctional nano-theranostic platform.

在肿瘤成像诊断的基础上即时进行微波热疗及对治疗效果进行实时监测，是当前生命分析和医学领域的研究热点。本项目拟设计合成具有协同治疗功能的离子液体，以克服现有微波热疗试剂安全性差及功能单一等问题，从而提高肿瘤的治疗效果。将设计合成的系列药物离子液体负载在成像探针修饰的二氧化硅空心纳米材料内，解决造影剂和微波热疗增敏剂难以有效组装的问题。并通过酸敏感键对纳米诊疗剂进行聚乙二醇功能化修饰，构建集各功能单元于一体的智能纳米诊疗试剂，提高其在肿瘤微酸性环境中富集效率和诊疗效果。系统探究基于离子液体的智能纳米诊疗剂在肿瘤成像和治疗中的应用潜力，为设计高效、多功能的纳米诊疗一体化平台提供理论支持和新的思路。

项目旨在设计多功能纳米复合材料，在疾病诊断和治疗之间搭起桥梁，构建新型纳米探针以及肿瘤诊疗平台。基于新型纳米材料，通过修饰、组装、复合，构建系列纳米探针，探索设计多种信号放大检测技术平台，使检测过程便捷、快速、灵敏，为生命分析应用的纳米材料设计提供新的思路。利用聚多巴胺表面修饰技术，一步法制备聚多巴胺包覆血红蛋白，解决血红蛋白氧载体氧化毒性的难题，降低血红蛋白自氧化，维持供氧效能，同时减轻在血红蛋白氧载体使用过程中导致的氧化损伤，避免不良反应的发生，为聚多巴胺在生物医学领域中的应用提供了理论参考。制备合成易于修饰、生物兼容性好的纳米复合材料，合理有效地组装功能原件，有针对性地将其递送到病变组织，提高治疗效果和减少对正常组织的毒副作用，进而实现肿瘤的有效治疗，对多功能纳米诊疗试剂的设计、构建具有一定的指导意义，为纳米材料在肿瘤诊疗领域的应用提供理论支持和新策略。