Xudong Liu,1,* Ye Liu,2,* Danyu Zhao,1 Dehong Shan,1 Chenghao Guo,3,4 Lianqun Jia1 

1College of Integrated Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, 116600, People’s Republic of China; 2Department of Nephrology, Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang, Liaoning Province, 110000, People’s Republic of China; 3Medical School of Yangzhou University, Yangzhou, Jiangsu Province, 225009, People’s Republic of China; 4Department of Urology, Ansteel Group General Hospital, Anshan, Liaoning Province, 617099, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lianqun Jia, Email il_lsl_phd@163.com

Abstract: Hepatocellular carcinoma (HCC) presents significant challenges due to its aggressive nature and resistance to conventional treatments. While CAR-T therapy has shown promise in hematologic cancers, its application in HCC is limited by the tumor microenvironment (TME), insufficient T-cell infiltration, and antigenic heterogeneity. Nanomaterials offer a promising solution by enhancing CAR-T cell delivery, activation, persistence, and overcoming the immunosuppressive TME. This review focuses on the application of nanoparticles in CAR-T therapy, highlighting recent advancements in nanomaterials-based mRNA delivery, photothermal remodeling, and hydrogel platforms. Furthermore, nanomaterials-enhanced imaging tools enable real-time monitoring of CAR-T cell activity, improving therapeutic precision and safety. By addressing current limitations, nanomaterial-mediated CAR-T therapy holds the potential to transform HCC treatment, paving the way for more effective and personalized cancer immunotherapy.

Keywords: nanomaterials, CAR-T, HCC, tumor microenvironment, immunotherapy