Nanomaterials Mediated Enhancement of CAR-T for HCC: Revolutionizing Immunotherapy Strategies

Int J Nanomedicine. 2025 Jun 13:20:7489-7500. doi: 10.2147/IJN.S527315. eCollection 2025.

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: CAR-T; HCC; immunotherapy; nanomaterials; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / therapy
  • Humans
  • Hydrogels / chemistry
  • Immunotherapy / methods
  • Immunotherapy, Adoptive* / methods
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / therapy
  • Nanoparticles / chemistry
  • Nanostructures* / chemistry
  • RNA, Messenger / administration & dosage
  • Receptors, Chimeric Antigen* / immunology
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / immunology

Substances

  • Receptors, Chimeric Antigen
  • Hydrogels
  • RNA, Messenger