Designing Two-Dimensional Nanosheets for Improving Drug Delivery to Fucose-Receptor-Overexpressing Cancer Cells.

Autor: Gupta N; School of Nano Sciences, Central University of Gujarat, Sector 30, Gandhinagar, Gujarat, 382030, India., Jangid AK; School of Nano Sciences, Central University of Gujarat, Sector 30, Gandhinagar, Gujarat, 382030, India., Singh M; School of Science, RMIT University, Melbourne, VIC, 3000, Australia., Pooja D; Applied Biology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India., Kulhari H; School of Nano Sciences, Central University of Gujarat, Sector 30, Gandhinagar, Gujarat, 382030, India.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2018 Dec 20; Vol. 13 (24), pp. 2644-2652. Date of Electronic Publication: 2018 Dec 06.
DOI: 10.1002/cmdc.201800575
Abstrakt: Targeted drug delivery has shown promise in improving the therapeutic efficacy of anticancer drugs. Gemcitabine hydrochloride (GEM) is a broad-range chemotherapeutic agent for the treatment of various cancers. However, systemic use of free GEM is restricted because of its poor physicochemical properties and nonspecific drug delivery, resulting in dose-dependent adverse effects. In this study, a fucose-conjugated graphene oxide (GO)-based smart targeted nanocarrier system was designed to provide high loading, sustained release, and targeted high concentrations of GEM to cancer cells. Fucose-conjugated GO nanosheets (FGONS) and GEM-loaded fucose-conjugated GO nanosheets (GEM-FGONS) were prepared and characterized by various techniques. About 36.2 % of GEM was loaded to the FGONS, which showed a pH-dependent release over a period of 48 h. A colloidal suspension of GEM-FGONS was found to be physiochemically stable for up to 96 h. In cytotoxicity studies, GEM-FGONS demonstrated time- and dose-dependent high toxicities on fucose-receptor-overexpressing MDA-MB-231 human breast cancer cells and A549 human lung cancer cells. Moreover, targeted formulations were more efficacious than non-targeted or free GEM. Overall, bioconjugation of fucose helps in the stabilizing and targeting of graphene oxide nanosheets.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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