Intraperitoneal ¹⁸⁸Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice

Background and purpose Cancer stem cells exhibit distinctive cellular metabolism compared with the more differentiated counterparts or normal cells. We aimed to investigate the impact of a novel radionuclide anti-cancer agent ¹⁸⁸Re-Liposome on stemness markers' expression and cellular metabolism in an ovarian cancer model. Material and methods A 2 × 2 factorial experiment was designed in which factor 1 represented the drug treatment comparing ¹⁸⁸Re-BMEDA, a free form of ¹⁸⁸Re, with ¹⁸⁸Re-Liposome, a nanoparticle-encapsulated form of ¹⁸⁸Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Results Intraperitoneal delivery of ¹⁸⁸Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of ¹⁸⁸Re-Liposome treatment was able to block epithelial-to-mesenchymal transition (EMT) and reactivate p53 function. Collectively, these molecular changes led to a striking tumour-killing effect. Conclusions Radionuclides encapsulated in liposomes may represent a novel treatment for ovarian cancer when delivered intraperitoneally (a type of loco-regional delivery). In the future, this concept may be further extended for the treatment of several relevant cancers that have been proved to be suitable for loco-regional delivery of therapeutic agents, such as colon cancer, gastric cancer, and pancreatic cancer.