1. Reverse poly(ε-caprolactone)-g-dextran graft copolymers. Nano-carriers for intracellular uptake of anticancer drugs.
- Author
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Delorme V, Lichon L, Mahindad H, Hunger S, Laroui N, Daurat M, Godefroy A, Coudane J, Gary-Bobo M, and Van Den Berghe H
- Subjects
- Antibiotics, Antineoplastic chemistry, Cell Line, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Doxorubicin chemistry, Drug Carriers chemistry, Drug Delivery Systems, Drug Screening Assays, Antitumor, HCT116 Cells, Humans, Micelles, Molecular Structure, Particle Size, Structure-Activity Relationship, Surface Properties, Antibiotics, Antineoplastic pharmacology, Dextrans chemistry, Doxorubicin pharmacology, Nanoparticles chemistry, Polyesters chemistry
- Abstract
A new fully biodegradable "reverse" oligosaccharide-based amphiphilic graft copolymer structure with a hydrophobic backbone and hydrophilic side chains, poly(ε-caprolactone)-g-dextran (PCL-g-Dex) was synthetized. For this purpose, "clickable" propargylated PCL (PCL-yne) and azido-dextran (Dex-N3) were prepared to further synthesize PCL-g-Dex copolymer by a Huisgen's cycloaddition. This "reverse" copolymer architecture self-assembled in biodegradable nano-carriers, in the shape of dynamic polymeric micelles, and were loaded with doxorubicin (Dox) anti-cancer drug. Dox-loaded micelles showed different drug releases depending on the pH. Cytotoxicity tests showed that Dox-loaded micelles can selectively kill colon cancer cells (HCT-116) while they have no cytotoxic effect towards healthy cells (CCD-45SK). Fluorescent micelles based on FITC-labelled PCL-g-Dex copolymer were used for fluorescence imaging and flow cytometry assays. These experiments proved the effective and specific internalization of micelles by cancer cells, whereas healthy cells showed a very poor uptake. These results show that PCL-g-Dex micelles may be a promising Dox nano-carrier in cancer chemotherapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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