NDLI: pH-sensitive polycarbonate micelles for enhanced intracellular release of anticancer drugs: a strategy to circumvent multidrug resistance

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pH-sensitive polycarbonate micelles for enhanced intracellular release of anticancer drugs: a strategy to circumvent multidrug resistance

Back cover

Polymer Chemistry Vol - 5 Issue - 6

Polymer Chemistry Vol - 5 Issue - 5

Polymer Chemistry Vol - 5 Issue - 4

Polymer Chemistry Vol - 5 Issue - 3

Polymer Chemistry Vol -4

Polymer Chemistry Vol -3

Polymer Chemistry Vol -2

Polymer Chemistry Vol -1

pH-sensitive polycarbonate micelles for enhanced intracellular release of anticancer drugs: a strategy to circumvent multidrug resistance

Content Provider	Royal Society of Chemistry (RSC)
Author	Hedrick, James L. Coady, Daniel J. Ke, Xiyu Yang, Yi Yan Yang, Chuan Engler, Amanda C.
Copyright Year	2014
Abstract	In this study, we have synthesized two novel amphiphilic diblock copolymers with aldehyde groups via organocatalytic ROP of a functionalized cyclic carbonate monomer (MTC-Bz) using polyethylene oxide (PEG) as the macroinitiator. The polymers were covalently conjugated with an anti-tumor drug doxorubicin (DOX) via a pH-sensitive Schiff-base linkage. The resulting conjugates formed micelles in phosphate-buffered saline (PBS) (pH 7.4) with an average size of about 100 nm and narrow size distribution. The surface charge of the micelles was close to zero. The micelles were stable in both PBS and cell culture media containing 10% FBS up to 5 days. The results obtained from the in vitro release study indicated that DOX release from the micelles was pH-dependent, being faster at pH 5.0 (the endolysosomal environment) than pH 7.4 (the extracellular environment). Human breast cancer MCF-7 cells and DOX-resistant MCF-7/Adr cells were employed to investigate the cellular uptake and cytotoxicity of DOX-loaded micelles. The confocal microscopy and flow cytometry studies showed that the uptake of DOX-loaded micelles by MCF-7 cells was similar to that of free DOX. In sharp contrast, the uptake of DOX-loaded micelles by MCF-7/Adr cells was significantly higher than that of free DOX. The polymers showed no toxicity to MCF-7 and MCF-7/Adr cells. The DOX-loaded micelles killed the cells efficiently. In particular, they were more potent against drug-resistant MCF-7/Adr cells than free DOX due to the higher cellular drug accumulation and pH-triggered intracellular drug release, providing a strategy to navigate around drug resistance. These DOX-conjugated micelles can be a promising carrier for the delivery of anticancer drugs with amine functional groups.
Starting Page	2621
Ending Page	2628
Page Count	8
File Format	HTM / HTML PDF
ISSN	17599954
Volume Number	5
Issue Number	7
Journal	Polymer Chemistry
DOI	10.1039/c3py01784b
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	PBS Cell culture Flow cytometry MCF-7 Cytotoxicity Confocal microscopy Breast cancer Aldehyde Doxorubicin Polyethylene glycol Amphiphile Monomer
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Bioengineering Biomedical Engineering Polymers and Plastics

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Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

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