Nano-Therapeutics for In Vivo Immune Cell Engineering.

Immune cell engineering, exemplified by chimeric antigen receptor T (CAR-T) cell therapy, has revolutionized the treatment of various diseases, particularly cancers. While significant advancements have been made in ex vivo immune cell editing, progress in in vivo engineering has been comparatively slower despite its substantial potential advantages, such as reduced manufacturing complexity and cost. However, in vivo approaches face critical challenges, including insufficient targeting specificity, limited editing efficiency, and uncertain long-term safety profiles. These limitations necessitate the exploration of nano-strategies to overcome biological barriers. This review summarizes the advantages of in vivo over ex vivo immune cell engineering, discusses the latest research progress in nano-therapeutics for in vivo immune cell engineering, and highlights applications across diverse diseases. Finally, we examine critical barriers hindering clinical translation and offer perspectives on future developments.