Authors
Siyu Meng, Xuan Wei, Ziyan Wang, Siyu Chen, Keying Chen, Jiamin Cheng, Zheng Chen, Jiabao Liang, Liangliang Dai
Published in
Advanced materials (Deerfield Beach, Fla.). Pages e74041. Jul 07, 2026. Epub Jul 07, 2026.
Abstract
Reversing the immunosuppressive tumor microenvironment by targeting metabolic competition between tumors and immune effector cells could induce tumor starvation and enhance the activity of immune cells, representing a potential approach to boost tumor immunotherapy. However, its actual efficacy is limited by compensatory oxidative phosphorylation (OXPHOS) energy replenishment and low delivery efficiency. Herein, we report a hydrogen sulfide (H2S)-self-supplying nanoplatform that orchestrates a dual blockade of glycolysis and OXPHOS for improved triple-negative breast cancer (TNBC) immunotherapy. The micellar system, HA-ADT@W, achieves tumor-targeted delivery of a glycolysis inhibitor (WZB117) and H2S continually released in GSH-overexpressed tumor cells. This strategy concurrently suppresses glucose uptake in tumor cells by reversing the acidic tumor microenvironment (TME) and disrupts compensatory OXPHOS via H2S-mediated inhibition of cytochrome c oxidase. Consequently, we demonstrate a significant rewiring of tumor energy metabolism that not only induces immunogenic cell death with remodeling of the immunosuppressive TME but also alleviates nutrient constraints of immune effector cells, leading to enhanced infiltration and function of cytotoxic immune cells. This work exhibits a smart nanoplatform-based H2S self-supplied micelle for reinforced TNBC immunotherapy via regulated metabolic competition between tumors and immune effector cells with TME normalization.
PMID:
42411917
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.
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