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Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
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Published on: April 30, 2021

H2S Self-Supplied Micelles Reverse Tumor-Immune Effector Cells Energy Metabolisms to Boost Breast Cancer

Siyu Meng1, Xuan Wei1, Ziyan Wang1

  • 1School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China.

Advanced Materials (Deerfield Beach, Fla.)
|July 7, 2026
PubMed

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.

Keywords:
H2S self‐supplied micelleOXPHOS and glycolysis suppressionimmunoregulationmetabolic reprogrammingtumor microenvironment remodeling

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