Nano meets CAR-T: A new era in cancer immunotherapy

Chimeric antigen receptor (CAR)-T cell immunotherapy is one of the emerging advancements in personalized treatment of cancer, whose design is based on the genetic modification of T cells to express chimeric antigen receptors (CARs) to generate CAR-T cells, specifically targeting cancer tissues. Despite the fact that immunotherapy provides significant antitumor activity, only a limited number of therapies reached the market after their FDA approval because of the accompanying challenges including tumor resistance, side effects, high cost of production, possible toxicities during CAR-T cells engineering, and poor selectivity. Nanotechnology has emerged as a promising approach for improving drug targeting, selectivity and reducing their side effects. In this context, recent advances highlight the innovative integration of nanomaterials for enhancing CAR-T cell engineering, delivery, and in vivo functionality. Nanotechnology-enabled strategies such as nanoparticle-based gene delivery systems, nanoformulations for controlled CAR expression, and tumor microenvironment modulation have demonstrated significant potential in overcoming current therapeutic limitations. Therefore, substantial research efforts are currently focused on integrating this technology in developing CAR-T cell immunotherapy. This review article focuses on CAR-T cell bioengineering, antitumor mechanism of action, challenges and limitations, as well as the latest innovative nanotechnological solutions for complementing CAR-T cell immunotherapy. It also emphasizes the translational applications and design innovations of nanotechnology, including precision targeting platforms and multifunctional nanocarriers, highlighting that nanotechnology may play an important role in advancing the efficacy, safety, and clinical applicability of personalized CAR-T cancer immunotherapy.