Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG (O) ) was developed to achieve cancer ozone therapy (O 3 -T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG (O) ) was prepared as a chemotherapeutic agent for local O 3 -T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG (O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O 3 -T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG (O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O 3 -T, especially for postoperative skin diseases.