pH-sensitive nanoparticles of poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate for anti-tumor drug delivery

被引：95
|
作者：
Li, Zhen [1 ,2 ]
Qiu, Lipeng [1 ]
Chen, Qing [1 ]
Hao, Tangna [3 ]
Qiao, Mingxi [1 ]
Zhao, Haixia [1 ]
Zhang, Jie [1 ]
Hu, Haiyang [1 ]
Zhao, Xiuli [1 ]
Chen, Dawei [1 ,4 ]
Mei, Lin [5 ,6 ]
机构：
[1] Shenyang Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, Shenyang 110016, Peoples R China
[2] Dalian Med Univ, Sch Pharm, Dalian 116044, Peoples R China
[3] Dalian Med Univ, Affiliated Hosp 2, Dept Pharm, Dalian 116011, Peoples R China
[4] Soochow Univ, Coll Med, Sch Pharm, Suzhou 215123, Peoples R China
[5] Tsinghua Univ, Grad Sch Shenzhen, Ctr Biotech & Biomed, Shenzhen Key Lab Gene & Antibody Therapy, Shenzhen 518055, Peoples R China
[6] Tsinghua Univ, Grad Sch Shenzhen, Div Life Sci, Shenzhen 518055, Peoples R China
来源：
ACTA BIOMATERIALIA | 2015年 / 11卷
关键词：
Doxorubicin; Copolymer nanoparticles; PH-sensitive; Multi-drug resistance; Cytotoxicity; VITAMIN-E TPGS; OVERCOMING MULTIDRUG-RESISTANCE; COPOLYMER MICELLES; INTRACELLULAR DELIVERY; PLGA NANOPARTICLES; POLYMERIC MICELLE; CANCER-TREATMENT; ANTICANCER DRUG; TUMOR PH; DOXORUBICIN;
D O I：
10.1016/j.actbio.2014.09.014
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
A novel pH-sensitive polymer, poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate (PLH-PLGA-TPGS), was synthesized to design a biocompatible drug delivery system for cancer chemotherapy. The structure of the PLH-PLGA-TPGS copolymer was confirmed by H-1-NMR, FTIR and GPC. The apparent pK(a) of the PLH-PLGA-TPGS copolymer was calculated to be 6.33 according to the acid-base titration curve. The doxorubicin (DOX)-loaded nanoparticles (PLH-PLGA-TPGS nanopartides and PLGA-TPGS nanoparticles) and corresponding blank nanoparticles were prepared by a co-solvent evaporation method. The blank PLH-PLGA-TPGS nanoparticles showed an acidic pH-induced increase in particle size. The DOX-loaded nanoparticles based on PLH-PLGA-TPGS showed a pH-triggered drug-release behavior under acidic conditions. The results of in vitro cytotoxicity experiment on MCF-7 and MCF-7/ADR cells showed that the DOX-loaded PLH-PLGA-TPGS nanoparticles resulted in lower cell viability versus the PLGA-TPGS nanoparticles and free DOX solution. Confocal laser scanning microscopy images showed that DOX-loaded PLH-PLGA-TPGS nanoparticles were internalized by MCF-7/ADR cells after 1 and 4 h incubation and most of them accumulated in lysosomes to accelerate DOX release under acidic conditions. In summary, the PLH-PLGA-TPGS nanoparticles have great potential to be used as carriers for anti-tumor drug delivery. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：137 / 150
页数：14
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