Nanoparticles-enhanced CAR-T cell therapy: current advances and future directions

Abstract Chimeric antigen receptor (CAR)-T cell therapy represents a revolutionary advancement in adoptive cellular immunotherapy, demonstrating remarkable efficacy against hematologic malignancies. However, its clinical application faces significant challenges: complex and costly production processes, limited therapeutic outcomes for solid tumors, and severe adverse reactions. Nanoparticles (NPs), with their tunable physicochemical properties, precise delivery capabilities, and multifunctional design, offer innovative solutions throughout the CAR-T therapy workflow. NPs enable more efficient and safer T-cell genetic engineering, enhance CAR-T cell homing and infiltration into solid tumors, actively remodel the immunosuppressive tumor microenvironment, and overcome antigen heterogeneity. Furthermore, NPs enable real-time monitoring of CAR-T cell spatiotemporal activity in vivo, opening novel avenues for therapeutic safety management. The review also explores the synergistic potential of artificial intelligence in optimizing NPs design, predicting therapeutic efficacy, and anticipating toxicity responses, laying the groundwork for developing more personalized NPs-based CAR-T therapy. Finally, we discuss the multifunctionality of NPs strategies in the other immune cell platforms, such as CAR-NK and CAR-macrophage cells.