Immunosuppressive Nanoparticles for Management of Immune-Related Adverse Events in Liver.

Abstract

Immune checkpoint blockade (ICB) therapy has been considered as an effective way to boost immune cells to recognize and attack tumors. However, side effects known as immune-related adverse events (irAEs) should be carefully managed. Here, we engineer immunosuppressive nanoparticles by coating PD-L1 overexpressed mesenchymal stem cells (MSCs) plasma membrane on poly lactic-<i>co</i>-glycolic acid nanoparticles (MSC-PD-L1⁺ NPs) for managing and reducing irAEs induced by immune checkpoint inhibitors. The nanoparticles can enrich at liver site after intravenous administration. In the high dose of anti-PD-L1 mAb-induced irAEs clinically relevant mouse model, a low dose of MSC-PD-L1⁺ NPs (2 mg/kg) sufficiently rescues hepatitis by inactivating T cells and macrophages in the liver tissue. More intriguingly, due to the dose threshold for nanoparticles to the tumor site, we unexpectedly find that the injected NPs do not affect the efficiency of ICB therapy to inhibit solid tumor growth. Such a strategy shows potential for managing the various cancer immunotherapy associated irAEs in clinical applications.