Allicin amplifies disulfidptosis during GOx catalyzing glucose-starvation for cancer therapy via simultaneous antimicrobial and antitumor intervention

Abstract

The intratumoral microbiota plays a crucial role in tumor progression, yet they are often disregarded when formulating cancer treatment strategies. The present study introduces a novel therapeutic approach targeting glucose utilization, and develops an acid-stable adhesive hydrogel co-loaded with glucose oxidase (GOx) and allicin (AG@G). This enables sustained and simultaneous intervention in tumor and bacterial proliferation within tumor. Allicin, a traditional Chinese medicine (TCM) extracted from garlic, exhibits dual efficacy by inhibiting both tumor growth and bacterial proliferation, while GOx catalyzes glucose consumption, depleting cellular energy reserves and initiating NADPH-mediated disulfidptosis. The synergistic combination of allicin and GOx amplifies intracellular disulfide stress and oxidative stress, effectively triggering disulfidptosis and ferroptosis. In vivo studies confirm the potent antitumor activity of AG@G, effectively suppressing the growth of tumor and associated microbiota in breast cancer, even in the drug-resistant lung cancer. Notably, AG@G treatment prevents lung metastasis of breast cancer and the homing of subcutaneous osimertinib-resistant lung cancer. This work suggests promising avenues for integrating traditional Chinese medicine in oncological treatment, and underscores the pivotal role of antibacterial strategies in cancer therapy.