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

Abstract

The molecular weight (Mw) 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 Mw of DXA without increasing its polydispersity. Prepared DXA derivatives (Mw = 10-185 kDa) have been conjugated to cisplatin and the Mw of the carrier found to have a significant impact on cisplatin release rates, in vitro cytotoxicity, and migrastatic potential. Conjugates with the high-Mw 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 Mw of DXA and amount of loaded cisplatin.

• Authors: L Münster, M Fojtů, M Muchová, F Latečka, S Káčerová, Z Capáková, T Juriňáková, I Kuřitka, M Masařík, J Vícha
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 272 Pg. 118461 (Nov 15 2021) ISSN: 1879-1344 [Electronic] England
• PMID: 34420721 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Dextrans
• Drug Carriers
• Nanogels
• Cisplatin

Topics

• A549 Cells
• Adenocarcinoma (drug therapy, metabolism)
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Movement (drug effects)
• Cisplatin (chemistry, pharmacology)
• Dextrans (chemistry)
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Female
• Humans
• Male
• Molecular Weight
• Nanogels (chemistry)
• Neoplasms (drug therapy, metabolism)
• Ovarian Neoplasms (drug therapy, metabolism)
• Oxidation-Reduction
• Prostatic Neoplasms (drug therapy, metabolism)