Stimuli-Responsive Nanozyme Reprograms Tumor Immunometabolism and Overcomes Therapeutic Resistance in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) exhibits profound glycolytic reprogramming that drives tumor growth, impairs apoptosis, and suppresses immune responses, leading to resistance against conventional therapies. To overcome this challenge, we developed a stimuli-responsive nanozyme composed of a pH-sensitive lipid-gelatin-protamine (LGP) nanogel encapsulating glucose oxidase (GOx). This tumor-selective nanozyme depletes intratumoral glucose under acidic conditions, inducing oxidative and endoplasmic reticulum stress, upregulating death receptors, and sensitizing HCC cells to TRAIL- and doxorubicin (DOX)-induced apoptosis. Co-delivery of GOx and DOX within the nanozyme reprograms tumor immunometabolism, enhancing immunogenic cell death and promoting the release of damage-associated molecular patt

SUBMITTER: Ta YN 

PROVIDER: S-EPMC12825357 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature