Yu Xin, Fang Chao, Zhang Kun, Su Chunxia
Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine, Shanghai 200092, China.
Pharmaceutics. 2022 Jul 29;14(8):1581. doi: 10.3390/pharmaceutics14081581.
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis showed remarkable improvements in overall response and patient survival, which changed the treatment landscape for multiple cancer types. However, the majority of patients receiving ICIs are either non-responders or eventually develop secondary resistance. Meanwhile, immunological homeostasis would be destroyed as T cell functions are activated excessively, leading to immune-related adverse events (irAEs). Clinically, a large number of irAEs caused by ICIs occurred and affected almost every organ system, resulting in the discontinuation or even the termination of the ongoing therapy. Therefore, researchers are exploring methods to overcome the situations of insufficient accumulation of these drugs in tumor sites and severe side effects. PD-1/PD-L1-targeted agents encapsulated in nanoparticles have emerged as novel drug delivery systems for improving the delivery efficacy, enhancing immune response and minimizing side effects in cancer treatment. Nanocarriers targeting the PD-1/PD-L1 axis showed enhanced functionalities and improved the technical weaknesses based on their reduced off-target effects, biocompatible properties, multifunctional potential and biomimetic modifications. Here, we summarize nanoparticles which are designed to directly target the PD-1/PD-L1 axis. We also discuss the combination of anti-PD-1/PD-L1 agents and other therapies using nanomedicine-based treatments and their anticancer effects, safety issues, and future prospects.
靶向PD-1/PD-L1轴的免疫检查点抑制剂（ICIs）在总体反应和患者生存率方面显示出显著改善，这改变了多种癌症类型的治疗格局。然而，大多数接受ICIs治疗的患者要么无反应，要么最终产生继发性耐药。与此同时，由于T细胞功能过度激活，免疫稳态会被破坏，导致免疫相关不良事件（irAEs）。临床上，由ICIs引起的大量irAEs发生，几乎影响到每个器官系统，导致正在进行的治疗中断甚至终止。因此，研究人员正在探索方法来克服这些药物在肿瘤部位蓄积不足和严重副作用的情况。封装在纳米颗粒中的靶向PD-1/PD-L1的药物已成为新型药物递送系统，用于提高递送效率、增强免疫反应并使癌症治疗中的副作用最小化。靶向PD-1/PD-L1轴的纳米载体基于其降低的脱靶效应、生物相容性、多功能潜力和仿生修饰，显示出增强的功能并改善了技术弱点。在此，我们总结了旨在直接靶向PD-1/PD-L1轴的纳米颗粒。我们还讨论了使用基于纳米医学的治疗方法将抗PD-1/PD-L1药物与其他疗法联合使用的情况及其抗癌效果、安全性问题和未来前景。
