State Key Laboratory of Natural Medicine, The School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China.
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China.
Biomaterials. 2023 Mar;294:122017. doi: 10.1016/j.biomaterials.2023.122017. Epub 2023 Jan 16.
The cancer photodynamic therapy (PDT) is limited by a congenital defect, namely the tumor hypoxia. Cancer cells are characterized by the vigorous oxygen-consuming glycolysis, which is well-known as the "Warburg effect" and one of the primary causes for the hypoxia. Herein, we employed the glucose metabolism as the cancer-specific target to enhance the performance of PDT. The Salvianolic acid B as the inhibitor of glucose uptake and aerobic glycolysis was concomitantly delivered with the photosensitizer chlorin e6 by a redox-responsive organosilica cross-linked micelle. The results demonstrated that the Salvianolic acid B suppressed the glucose metabolism, retarded the oxygen consumption to retain adequate oxygen as the ammo for PDT, which remarkably improve the efficacy of PDT both in vitro and in vivo. Our study not only provides an alternative strategy to address the hypoxia problem for PDT, but also enhances the selectivity of the treatment by targeting the cancer-specific Warburg effect.
癌症的光动力疗法（PDT）受到一个先天缺陷的限制，即肿瘤缺氧。癌细胞的特征是耗氧旺盛的糖酵解，这就是众所周知的“Warburg 效应”，也是导致缺氧的主要原因之一。在这里，我们将葡萄糖代谢作为癌症的特异性靶点，以增强 PDT 的性能。丹酚酸 B 作为葡萄糖摄取和有氧糖酵解的抑制剂，通过氧化还原响应的有机硅交联胶束与光敏剂叶绿酸 e6 同时递送。结果表明，丹酚酸 B 抑制了葡萄糖代谢，减缓了氧气消耗，为 PDT 保留了足够的氧气作为弹药，从而显著提高了体外和体内 PDT 的疗效。我们的研究不仅为 PDT 的缺氧问题提供了一种替代策略，而且通过针对癌症特异性的 Warburg 效应提高了治疗的选择性。
