量子点光催化产CO增敏肿瘤免疫/光热多模式联合治疗

Current cancer therapy is still suffered from low therapeutic efficacy and high risk of side effect. In this project, we aim to design and construct a novel multi-mode synergetic anti-tumor strategy based on combined photocatalytic CO gas therapy/CIT/PTT. The controlled release of CO gas can be achieved through in-situ photocatalytic CO2 reduction in vivo. More importantly, by virtue of the merits of CO in sensitizing tumor cells, the CO gas therapy, CIT, and PTT can be effectively combined together to provide more safety and effective solution for cancer treatment. The main contents in this project are as follows: (1) Designing and constructing perovskite dot-based Cs3Bi2Br9@Bi2S3 nanomedicine with high photocatalytic CO2 reduction activity and high selectivity toward CO by combining experimental research and DFT theoretical simulation calculations; (2) Modifying the surface of Cs3Bi2Br9@Bi2S3 with FAL peptides to endow the endoplasmic reticulum-targeting ability; (3) Establishing the newly multi-mode anti-tumor model of photocatalytic CO gas/CIT/PTT, and studying the combined therapy effect and synergistic mechanism. The implementation of this project will pave the way for the synergistic mechanism research of CO gas therapy as well as CIT and PTT, and provide a new strategy for safe and efficient clinic application of multimodal photocatalytic CO gas/CIT/PTT therapeutic nanoplatform.

针对当前癌症治疗疗效低、毒副作用大的问题，本项目拟开展基于光催化CO气体增敏的CIT/PTT多模式联合抗肿瘤新策略的研究。通过原位光催化CO2还原，实现CO的体内可控释放。并利用CO在抗肿瘤以及敏化癌细胞方面的优势，实现CO气体治疗与CIT以及PTT的联合。具体地：（1）通过实验与理论模拟计算相结合的方式，设计构建具有高CO2光催化还原活性与高CO选择性的Cs3Bi2Br9@Bi2S3核壳结构量子点纳米药物；（2）经FAL多肽靶向性修饰，实现光催化CO气体增敏的CIT/PTT多模式联合诊疗纳米平台的构建；（3）深入考察和研究光催化CO气体治疗与CIT以及PTT三者间的联合治疗效果与协同作用机制。本申请项目的实施，将为CO气体治疗与CIT以及PTT的联合作用机制研究提供新的方法，为光催化CO气体增敏的CIT/PTT多模式联合抗肿瘤临床应用提供理论基础，具有重要的科学意义和应用前景。

本项目主要针对当前癌症治疗疗效低、毒副作用大的问题，开展基于光催化CO气体增敏的多模式联合抗肿瘤新策略的研究。通过体内原位光催化CO2还原，实现CO的可控释放，并利用CO在抗肿瘤以及敏化癌细胞方面的显著优势，实现CO气体治疗与免疫治疗以及光热治疗的联合。项目较好地完成了原定计划，在CO2还原光催化剂的研发、CO选择性提升、光催化机制揭示、肿瘤免疫治疗等研究内容上，均取得了不错的研究进展与科研成果，并基本建立了基于体内原位光催化CO气体增敏的多模式联合抗肿瘤新策略的研究：(1)实现了生理稳定性好、生物安全性高，并拥有出色的体内成像、体内原位光催化CO产生，以及光热转换能力的新型钙钛矿量子点基纳米药物的可控合成。(2)通过先进原位表征技术、体外活性测试，以及DFT理论模拟计算等手段，明确了合成工艺条件与材料构效关系间的联系，揭示了“材料制备工艺—材料微结构与电子结构—材料性能”间的作用机制。(3)通过体外实验、细胞实验、动物实验以及活体成像技术，掌握了药物的体内运输与靶向行为。(4)推动了肿瘤免疫治疗新模式的发展，为肿瘤多模式联合治疗的实际临床应用提供了基础性数据支撑。