Enhancing cisplatin anticancer effectivity and migrastatic potential by modulation of molecular weight of oxidized...

The molecular weight (M_w) of dextran derivatives, such as regioselectively oxidized dicarboxydextran (DXA), is greatly influencing their faith in an organism, which could be possibly used to improve anticancer drug delivery. Here we present a modified method of sulfonation-induced chain scission allowing direct and accurate control over the M_w of DXA without increasing its polydispersity. Prepared DXA derivatives (M_w = 10-185 kDa) have been conjugated to cisplatin and the M_w of the carrier found to have a significant impact on cisplatin release rates, in vitro cytotoxicity, and migrastatic potential. Conjugates with the high-M_w DXA showed particularly increased anticancer efficacy. The best conjugate was four times more effective against malignant prostatic cell lines than free cisplatin and significantly inhibited the ovarian cancer cell migration. This was traced to the characteristics of spontaneously formed cisplatin-crosslinked DXA nanogels influenced by M_w of DXA and amount of loaded cisplatin.