Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery

	Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery
	Cheng R ; Meng FH ; Ma SB ; Xu HF ; Liu HY ; Jing XB ; Zhong ZY
刊名	journal of materials chemistry
	2011
卷号	21 期号:47 页码:19013-19020
关键词	CYTOCHROME-C OXYGEN CARRIER ENCAPSULATED HEMOGLOBIN DRUG-DELIVERY APOPTOSIS VESICLES VEHICLES THERAPEUTICS NANOCARRIERS NANOREACTOR
ISSN号	0959-9428
通讯作者	zhong zy
中文摘要	the study of biological functions of proteins in cells as well as therapeutic exploration of many protein drugs demands efficient and nontoxic intracellular protein delivery systems. herein, reduction and temperature dual-responsive crosslinked polymersomes were developed for the facile encapsulation of various proteins under mild conditions as well as rapid release of proteins in cancer cells. two thermo-sensitive triblock copolymers, peg(5k)-paa(1.7k)-pnipam(22k) and peg(5k)-paa(0.7k)-pnipam(12k) (denoted as polymer 1 and 2, respectively), were prepared by controlled reversible addition-fragmentation chain-transfer (raft) polymerization. interestingly, polymers 1 and 2 exhibited lower critical solution temperatures (lcst) of 39 and 38 degrees c in pbs (ph 7.4, 20 mm, 150 mm nacl) and 34 and 32 degrees c in mes (ph 5.5, 20 mm), respectively. increasing the temperature of polymer solutions in mes to 40 degrees c yielded robust polymersomes with average diameters of ca. 150 similar to 170 nm following crosslinking the paa segment with cystamine (cys) via carbodiimide chemistry. these crosslinked polymersomes kept their structures in pbs at 37 degrees c but rapidly dissociated into unimers in response to 10 mm dithiothreitol (dtt). remarkably, various proteins including bovine serum albumin (bsa), lysozyme (lys), cytochrome c (cc), and ovalbumin (ova) could be conveniently loaded into the polymersomes with markedly high protein loading efficiencies of 60 similar to 100% at theoretical protein loading contents of 10 similar to 50 wt%. the in vitro release studies using cys-crosslinked polymersome 1 showed that release of bsa, lys, and cc was minimal (ca. 20%) in 11 h in pbs at 37 degrees c, while fast protein release of over 70% was observed under an intracellular mimicking reductive environment. mtt assays revealed that these polymersomes were practically non-toxic to hela and mcf-7 cells up to a tested concentration of 200 mu g ml(-1). confocal laser scanning microscope (clsm) observations showed that fitc-cc loaded cys-crosslinked polymersomes efficiently delivered and released fitc-cc into the cytosol of mcf-7 cells after 12 h incubation. in contrast, little fitc-cc fluorescence was observed in mcf-7 cells treated with free fitc-cc as well as fitc-cc loaded 1,4-butadiamine crosslinked polymersomes (reduction-insensitive control). flow cytometry studies showed that cc loaded cys-crosslinked polymersomes induced markedly enhanced apoptosis of mcf-7 cells as compared to free cc and the reduction-insensitive controls. these novel reduction and temperature dual-responsive crosslinked polymersomes have opened a new avenue to targeted intracellular protein delivery.
语种	英语
WOS记录号	WOS:000297265800020
公开日期	2012-06-11
内容类型	期刊论文
源URL	[http://ir.ciac.jl.cn/handle/322003/44900]
专题	长春应用化学研究所_长春应用化学研究所知识产出_期刊论文
推荐引用方式 GB/T 7714	Cheng R,Meng FH,Ma SB,et al. Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery[J]. journal of materials chemistry,2011,21(47):19013-19020.
APA	Cheng R.,Meng FH.,Ma SB.,Xu HF.,Liu HY.,...&Zhong ZY.(2011).Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery.journal of materials chemistry,21(47),19013-19020.
MLA	Cheng R,et al."Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery".journal of materials chemistry 21.47(2011):19013-19020.