Co-delivery of oxaliplatin and demethylcantharidin via a polymer-drug conjugate.
A Pt (IV) complex which combined the bioactivities of both oxaliplatin and demethylcantharidin (DMC) is synthesized and delivered by a polymer-drug conjugate for combination chemotherapy. Oxaliplatin is released from the polymer-drug conjugate within cancer cell by reduction to attack nuclear DNA, while a dose of DMC is also hydrolyzed subsequently to block DNA damage-induced defense mechanisms by serine/threonine phosphatase 2A (PP2A) inhibition. In vitro evaluation shows that the polymer-drug conjugate with dual modes of action upon cancer cells displays higher cytotoxicity against SKOV-3 cells than that of free drugs. This enhanced cytotoxicity is attributed to the synergistic effect between oxaliplatin and DMC, as well as the effective intracellular internalization of the micelles observed by confocal laser scanning microscopy (CLSM) imaging.
['Wang|Enhui|E|', 'Xiong|Hejian|H|', 'Zhou|Dongfang|D|', 'Xie|Zhigang|Z|', 'Huang|Yubin|Y|', 'Jing|Xiabin|X|', 'Sun|Xinhua|X|']
D002193:Cantharidin D045744:Cell Line, Tumor D006801:Humans D008823:Micelles D018613:Microscopy, Confocal D009369:Neoplasms D009944:Organoplatinum Compounds D000077150:Oxaliplatin D011108:Polymers
co-delivery oxaliplatin polymer-drug conjugate combination chemotherapy PP2A inhibition