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

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.

Automated summary

The study presents an improved method of sulfonation-induced chain scission for direct and accurate control over the molecular weight of DXA derivatives. It reveals that conjugates with high-M-w DXA show increased anticancer efficacy, with the best conjugate being four times more effective against malignant cells than free cisplatin and significantly inhibiting cancer cell migration. The characteristics of spontaneously formed cisplatin-crosslinked DXA nanogels influenced by the M-w of DXA and amount of loaded cisplatin contribute to these findings.