کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10159217 39 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Reduction and pH dual-bioresponsive crosslinked polymersomes for efficient intracellular delivery of proteins and potent induction of cancer cell apoptosis
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Reduction and pH dual-bioresponsive crosslinked polymersomes for efficient intracellular delivery of proteins and potent induction of cancer cell apoptosis
چکیده انگلیسی
The clinical applications of protein drugs are restricted because of the absence of viable protein delivery vehicles. Here, we report on reduction- and pH--sensitive crosslinked polymersomes based on the poly(ethylene glycol)-poly(acrylic acid)-poly(2-(diethyl amino)ethyl methacrylate) (PEG-PAA-PDEA) triblock copolymer for efficient intracellular delivery of proteins and the potent induction of cancer cell apoptosis. PEG-PAA-PDEA (1.9-0.8-8.2 kg mol−1) was synthesized by controlled reversible addition-fragmentation chain transfer polymerization and further modified with cysteamine to yield the thiol-containing PEG-PAA(SH)-PDEA copolymer. PEG-PAA(SH)-PDEA was water-soluble at acidic and physiological pH but formed robust and monodisperse polymersomes with an average size of ∼35 nm upon increasing the pH to 7.8 or above followed by oxidative crosslinking. These disulfide-crosslinked polymersomes, while exhibiting excellent colloidal stability, were rapidly dissociated in response to 10 mM glutathione at neutral or mildly acidic conditions. Notably, these polymersomes could efficiently load proteins like bovine serum albumin and cytochrome C (CC). The in vitro release studies revealed that protein release was fast and nearly quantitative under the intracellular-mimicking reducing environment. Confocal microscopy observations showed that these dual-sensitive polymersomes efficiently released fluorescein isothiocyanate-CC into MCF-7 cells in 6 h. Most remarkably, MTT assays showed that CC-loaded dual-sensitive polymersomes induced potent cancer cell apoptosis, in which markedly decreased cell viabilities of 11.3%, 8.1% and 52.7% were observed for MCF-7, HeLa and 293T cells, respectively, at a CC dosage of 160 μg ml−1. In contrast, free CC caused no cell death under otherwise the same conditions. These dual-bioresponsive polymersomes have appeared as a multifunctional platform for active intracellular protein release.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Biomaterialia - Volume 10, Issue 5, May 2014, Pages 2159-2168
نویسندگان
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