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Construction of a Drug Delivery System via pH-Responsive Polymeric Nanomicelles Containing Ferrocene for DOX Release and Enhancement of Therapeutic Effects
[Image: see text] We report an amphiphilic block copolymer via poly(ethylene glycol) methyl ether-D(labile)-poly(caprolactone)-ferrocene (mPEG-D(labile)-PCL-Fc) to deliver anticancer drug doxorubicin (DOX). Lipase Novozyme-435 was used as a catalyst for ring-opening polymerization with ε-caprolacton...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552479/ https://www.ncbi.nlm.nih.gov/pubmed/34723021 http://dx.doi.org/10.1021/acsomega.1c04330 |
Sumario: | [Image: see text] We report an amphiphilic block copolymer via poly(ethylene glycol) methyl ether-D(labile)-poly(caprolactone)-ferrocene (mPEG-D(labile)-PCL-Fc) to deliver anticancer drug doxorubicin (DOX). Lipase Novozyme-435 was used as a catalyst for ring-opening polymerization with ε-caprolactone, and an acid-sensitive Schiff base was used to connect the hydrophilic and hydrophobic parts; the ferrocene provided ferrous ions and was introduced at the end of the amphiphilic copolymer. The resulting copolymers were characterized by (1)H NMR/(13)C NMR and could be self-assembled in an aqueous solution to form nanomicelles with PCL-Fc as a hydrophobic core and mPEG as a hydrophilic shell. Transmission electron microscopy showed that the micelles were spherical and nanosized before and after DOX loading. The blank micelles also showed good biocompatibility. The drug-loaded polymeric nanomicelles exhibited a positive anticancer effect relative to the copolymers without ferrocene; the therapeutic effect of drug-loaded micelles containing ferrocene was more obvious. In vitro drug release results also showed that the polymer had a good pH response. Confocal microscopy also showed that polymeric micelles can effectively deliver and release the drug; the polymer containing ferrocene also leads to significantly improved ROS levels in tumor cells. Ferrocene can effectively and synergistically inhibit tumor cells with DOX. |
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