Nanotechnology-enhanced CAR-T therapy strategies in cancer, aging, and autoimmune diseases

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a transformative immunotherapy, which achieves remarkable success in hematological malignancies. However, broader application of CAR-T therapy is hindered by multiple challenges, including limited efficacy in solid tumors, antigen escape, severe toxicities, and complex, costly manufacturing. Recent studies have emerged that nanotechnology offers innovative solutions to overcome barriers. In this review, we summarized how nanotechnology enhances CAR-T therapy across six dimensions: CAR design, transfection, expansion, modification, monitoring, and combination with other therapies. We discussed the applications of various nanomaterials to improve CAR-T cell function, including lipid nanoparticles, nanogels, and nanobodies. Specifically, we recapitulate that nanotechnology facilitates the generation of CAR-T cells in vivo, enables spatiotemporal control of T cells, remodels the immunosuppressive microenvironment in solid tumors, and enables dual-targeting strategies to mitigate antigen escape. Finally, we outlined the clinical application of nanotechnology in hematological malignancies and solid tumors, as well as non-malignant senescence and autoimmune diseases. Collectively, we believe the integration of nanotechnology enhances the safety and efficacy and broadens therapeutic scope, which will open a new era of precision medicine.