Recent Advances in Nanoparticles-Based Platforms Targeting the PD-1/PD-L1 Pathway for Cancer Treatment

Abstract

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.

Keywords: PD-1/PD-L1; cancer immunotherapy; delivery nanoplatforms; immune checkpoint; nanoparticles.

Figure 1

A comparison of ICIs alone and NPs loading ICIs. The application of ICIs leads to the activation of tumor-specific T cells by blocking PD-1 and CTLA-4 on T cells and also PD-L1/2 on tumor cells or APCs as well. The administration of ICIs alone over-stimulates the immune system and increases the possibility of off-target effects which is the cause of systemic AEs. By contrast, NPs loading ICIs leads to a high local concentration of ICIs in the tumor site while reducing the off-target side effects.

Figure 2

A scheme to illustrate the rationale strategies combining PD-1/PD-L1 blockers with other therapies using nanoplatforms. PDT, photodynamic therapy; PTT, photothermal therapy; NPs, nanoparticles.