Photothermal targeting of lactate metabolism reverses radioresistance via disrupting the immunosuppressive barrier.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42437536.
- Also identified by DOI 10.1016/j.biomaterials.2026.124430.
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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.