Enhancing cisplatin anticancer effectivity and migrastatic potential by modulation of molecular weight of oxidized dextran carrier
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
34420721
DOI
10.1016/j.carbpol.2021.118461
PII: S0144-8617(21)00848-1
Knihovny.cz E-resources
- Keywords
- Carrier, Cisplatin, Dextran, Drug-delivery, Molecular weight, Periodate oxidation,
- MeSH
- Adenocarcinoma drug therapy metabolism MeSH
- A549 Cells MeSH
- Cisplatin chemistry pharmacology MeSH
- Dextrans chemistry MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Molecular Weight MeSH
- Prostatic Neoplasms drug therapy metabolism MeSH
- Ovarian Neoplasms drug therapy metabolism MeSH
- Neoplasms drug therapy metabolism MeSH
- Nanogels chemistry MeSH
- Drug Carriers chemistry MeSH
- Oxidation-Reduction MeSH
- Cell Movement drug effects MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cisplatin MeSH
- Dextrans MeSH
- Nanogels MeSH
- Drug Carriers MeSH
- Antineoplastic Agents MeSH
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.
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