Lymph Node-Targeting Nanotherapy Combined with Photothermal Therapy to Potentiate Chimeric Antigen Receptor-T Cell Treatment of Oral Cancer.

Authors

Zihui Ni, Yuanyuan Li, Xiangxiang Huang, Fanrui Zeng, Jiarong Zhang, Ben Zhong Tang, Laikui Liu, Ming Zhang

Published in

ACS nano. Jul 02, 2026. Epub Jul 02, 2026.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the head and neck. Immunotherapy has emerged as a promising treatment option for metastatic OSCC because of its potential clinical benefits; however, its effectiveness is limited by the immunosuppressive tumor microenvironment (TME), short-lived responses, and poor infiltration. To overcome these issues, we developed a strategy that combines photothermal therapy (PTT) with chimeric antigen receptor (CAR)-T cell immunotherapy. The prepared conjugated polymer nanoparticles (CPNPs) serve as efficient near-infrared-II (NIR-II) photothermal agents, enabling localized PTT and triggering strong immunogenic cell death (ICD) to activate T cells. Moreover, we engineered a lymph node-targeting nanosystem (ApoA1@PNPs) to improve in vivo production of CAR-T cells. Mucin 1 (MUC1)-specific CAR-T cells were designed to enhance tumor antigen recognition. This combined approach helps CAR-T cells reach primary tumor sites more effectively and induces long-lasting systemic immunity. By addressing the main limitations of traditional CAR-T therapy in OSCC, our integrated PTT/CAR-T strategy offers a potential therapeutic approach with significant clinical potential. This dual method aims to improve patient outcomes by achieving better tumor control.

PMID:
42391550
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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