| Summary: | 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.
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