1. Lactate/Cysteine Dual-Consuming Probiotic-Nanomedicine Biohybrid System for Enhanced Cancer Chemo-Immunotherapy.
- Author
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Xie TQ, Yan X, Qin YT, Zhang C, Jin XK, Li QR, Rao ZY, Zhou H, Chen WH, and Zhang XZ
- Subjects
- Animals, Mice, Humans, Doxorubicin pharmacology, Doxorubicin chemistry, Doxorubicin therapeutic use, Neoplasms therapy, Neoplasms immunology, Neoplasms drug therapy, Nanomedicine methods, Cell Line, Tumor, Glutathione metabolism, Glutathione chemistry, Immunotherapy methods, Probiotics therapeutic use, Cysteine chemistry, Lactic Acid chemistry, Nanoparticles chemistry, Nanoparticles therapeutic use
- Abstract
Immunotherapy is revolutionizing oncology, but its therapeutic efficiency is still limited by the off-target toxicities and poor antitumor immune responses. By integrating the drug-loaded nanoparticles (DMnSH) with the unique metabolic traits of Veillonella parvula (Vei), a probiotic-nanomedicine conjugate Vei@DMnSH biohybrid is elaborately designed for enhanced cancer chemo-immunotherapy. Specifically, Vei@DMnSH can accumulate in hypoxic tumor sites and simultaneously consume lactate and cysteine to reverse the lactate-associated immunosuppression and impede the biosynthesis of GSH. In addition, the DMnSH nanoparticles will rapidly deplete intracellular GSH and disassemble to release DOX and Mn
2+ . Accompanied by the two-pronged GSH depletion, the Mn2+ -mediated Fenton-like reaction can effectively generate oxidative hydroxyl radicals to induce heavy redox imbalance. Combined with the therapeutic effect of DOX, robust immunogenic cell death is provoked and subsequently activates antitumor adaptive immunity with a tumor suppression rate over 82%, synergistically enhancing the therapeutic outcomes of cancer chemo-immunotherapy.- Published
- 2024
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