光动力联合免疫检查点抑制剂治疗恶性肿瘤的研究进展

Research Progress of Photodynamic Combined Immune Checkpoint Inhibitors in the Treatment of Malignant Tumors

摘要

恶性肿瘤严重危害人体健康，光动力疗法是一种集创伤小、副作用低、时空可控性高等优点于一身的新兴疗法，被广泛应用于恶性肿瘤的临床治疗，但其只限于局部肿瘤的治疗，对于远处转移的肿瘤或无法精确定位的病灶，光动力疗法具有一定的局限性。免疫治疗尤其是免疫检查点抑制剂，使恶性肿瘤的治疗进入了一个全新的时代，然而免疫检查点在肿瘤细胞中的低表达水平及其对宿主免疫系统的激活不足构成主要障碍。光动力治疗可以激活机体的免疫功能，改善肿瘤微环境，这为光动力疗法与免疫疗法相结合提供了可能。而纳米粒子可以同时负载光敏剂和免疫检查点抑制剂，实现联合治疗效果，并提高药物的靶向性。本文对利用纳米技术将光动力与免疫检查点抑制剂相结合治疗恶性肿瘤的实验研究进行了综述，并对其在临床上的应用进行了展望。

Abstract

Malignant tumors are seriously harmful to human health. Photodynamic therapy is an emerging therapy with advantages of low trauma, low side effects and high spatiotemporal control. It has been widely used in the clinical treatment of malignant tumors, but it is limited to the treatment of local tumors. For distant metastatic tumours or lesions that cannot be precisely located, photodynamic therapy has certain limitations. Immunotherapy, especially immune checkpoint inhibitors, has brought the treatment of malignant tumors into a new era. However, the low expression level of immune checkpoint in tumor cells and its insufficient activation of the host immune system constitute major obstacles. Photodynamic therapy can activate the immune function of the body and improve the tumor microenvironment, which provides a possibility for the combination of photodynamic therapy and immunotherapy. Nanoparticles can simultaneously load photosensitizers and immune checkpoint inhibitors to achieve combined therapeutic effect and improve drug targeting. In this paper, the experimental research on the combination of photodynamic and immune checkpoint inhibitors using nanotechnology in the treatment of malignant tumors is reviewed. And its clinical application is prospected.

Graphical abstract

关键词

光动力疗法 / PD-1/PD-L1 / CTLA-4 / 联合治疗 / 纳米载药粒子

Key words

photodynamic therapy / PD-1/PD-L1 / CTLA-4 / combination therapy / nano drug-carrying particles

基金资助

国家自然科学基金(61875113)

量子光学与光量子器件国家重点实验室开放课题(KF202002)