Photothermal targeting of lactate metabolism reverses radioresistance via disrupting the immunosuppressive barrier.

Authors

Hongpei Deng, Liyang Zhou, Hao Tian, Huimin Lin, Liang Ma, Bo Ma, Feng Wang, Zixuan Gao, Shengfang Ge, Chuanbin Mao, Daxiang Cui, Jing Ruan

Published in

Biomaterials. Volume 336. Pages 124430. Jul 08, 2026. Epub Jul 08, 2026.

Abstract

Radiotherapy (RT) is frequently compromised by radioresistance and insufficient immunogenicity. Multiomics analysis here identifies a significant association between glycolysis and DNA damage repair, linking them to RT resistance and poor patient survival. To address this, we develop a mild thermia-guided radiosensitizer, GQD@PDA/Au, which reprograms glycolytic metabolism upon photothermal stimulation to inhibit lactate accumulation. Reduced lactate levels aggravate DNA damage and dsDNA breaks, thereby enhancing tumor radio-immunogenicity by activating the cGAS-STING pathway, inducing tumor ICD, and facilitating dendritic cell maturation. This work develops a clinically translatable platform that overcomes RT resistance and augments antitumor immunity via mild thermia-responsive radiosensitization.

PMID:
42437536
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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