Abstract：
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 (O3-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 O3-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 O3-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 O3-T, especially for postoperative skin diseases.
摘要：
在恶性细胞中发生的广泛的细胞成分引发的有效化学反应可能有助于探索癌症治疗的新兴策略。在这里，开发了一种臭氧化油凝胶（OG（O）），以实现基于细胞内Criegee反应的癌症臭氧治疗（O3-T）。通过整合化疗药物，制备了负载臭氧的油凝胶（Dox@OG（O））作为局部O3-T的化学治疗剂，与化疗（CT）/放疗（RT）/免疫治疗和伤口愈合相关。体外结果表明,Dox@OG（O）可以实现较高的臭氧加载效率并确保其稳定性。这种油凝胶介导的O3-T可以通过细胞膜上发生的细胞内Criegee反应直接破坏肿瘤细胞，以及通过产生氧/活性氧（ROS）和消耗谷胱甘肽（GSH）来调节肿瘤微环境（TME）的作用。同时,在X光的刺激下,观察到自由基的产生加速，进一步结合TME调节后的无线电灵敏度，将达到有效的抗肿瘤效果。更进一步,体内结果表明，局部植入的Dox@OG（O）可以有效抑制原发性和继发性肿瘤的生长。考虑到上述这些结果，它将作为未来研究O3-T的灵感，尤其是术后皮肤病。
