@article{Sun2026, 
author = {Bixi Sun and Yiming Qi and Haichao Zhu and Chenming Zou and Zhaozhong Wang and Chenfeng Wang and Yuepeng Tang and Yiyang Xia and Derong Cui and Zhu Jin and Feihu Wang and Shengrong Guo},
title = {Synergistical treatment of TNBC with nanogels via disrupting glycolysis, inducing ICD and ferroptosis},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {2},
pages = {94908349},
keywords = {triple-negative breast cancer, ferroptosis, immunogenic cell death, three-in-one nanogels, glycolysis disruption},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908349},
doi = {10.26599/NR.2026.94908349},
abstract = {Triple-negative breast cancer (TNBC) presents formidable therapeutic challenges due to its triple defense system including antioxidant capacity, glycolytic metabolism, and immunosuppressive microenvironment. To overcome these interconnected resistance mechanisms, we developed a multifunctional nanogel (3-in-1 NG) consisting of Fe2+-crosslinked boronate-conjugated mannose-alginate with encapsulated D-α-tocopheryl polyethylene glycol succinate (TPGS), which enables efficient tumor delivery. 3-in-1 NG achieved a 52.9% tumor growth inhibition rate and significantly impeded metastatic progression in 4T1 models. Mechanistically, the pH-triggered mannose release led to intracellular accumulation of mannose-6-phosphate. This effectively blocked glycolytic activity and reversed immunosuppressive lactate accumulation, priming tumors for ferroptosis. The nanoplatform simultaneously executes therapeutic functions including metabolic disruption via mannose-mediated glycolysis inhibition, TPGS-induced immunogenic cell death triggering dendritic cell maturation and cytotoxic T-cell infiltration, and Fe2+-dependent lipid peroxidation initiating ferroptosis cascade. These synergistic mechanisms established self-reinforcing therapeutic actions where metabolic inhibition enhanced both immune recognition and ferroptosis susceptibility, creating a feed-forward cycle that progressively dismantled tumor defenses. Our work pioneers a nanomedicine strategy that simultaneously exploits the metabolic plasticity, redox adaptability, and immune escape of TNBC, providing a unified synergistic solution for refractory malignancies.}
}