pH-sensitive pullulan-based nanoparticle carrier for adriamycin to overcome drug-resistance of cancer cells

被引:40
|
作者
Guo, Hua [1 ]
Liu, Yuanyuan [1 ,2 ,3 ]
Wang, Yan [2 ,3 ]
Wu, Jing [1 ,4 ]
Yang, Xiaoying [2 ,3 ]
Li, Rongshan [2 ,3 ]
Wang, Yinsong [2 ,3 ]
Zhang, Ning [1 ,2 ,3 ]
机构
[1] Tianjin Med Univ, Canc Inst & Hosp, Canc Cell Biol Lab, Natl Clin Res Ctr Canc,Key Lab Canc Prevent & The, Tianjin 300060, Peoples R China
[2] Tianjin Med Univ, Tianjin Key Lab Technol Enabling Dev Clin Therape, Sch Pharm, Tianjin 300070, Peoples R China
[3] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China
[4] Tianjin Third Cent Hosp, Tianjin 300170, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
O-Urocanyl pullulan; pH-sensitive; Nanoparticle carrier; Drug resistance; Cancer; MULTIDRUG-RESISTANCE; TUMOR PH; GLYCOPROTEIN; MECHANISMS; STRATEGIES; DELIVERY; BIODISTRIBUTION; CYTOTOXICITY; CONJUGATE; TRANSPORT;
D O I
10.1016/j.carbpol.2014.05.057
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
Urocanic acid was conjugated to pullulan to synthesize O-urocanyl pullulan (URPA) with degree of substitution (DS) of 8.2%. URPA nanoparticles prepared by dialysis method had spherical shapes and a mean diameter of 156.8 +/- 16.8 nm. Adriamycin (ADR) was successfully loaded into URPA nanoparticles and exhibited pH-sensitive in vitro release property. KIT assay showed that ADR-loaded URPA (ADR/URPA) nanoparticles had a significant higher toxicity against drug resistant MCF-7/ADR cells than free ADR, and the reversal index reached up to 9.6. The results of flow cytometry and confocal microscopy showed that URPA nanoparticles efficiently enhanced accumulation and retention of ADR in MCF-7/ADR cells and successfully delivered ADR into cell nucleus. The reversal effect of ADR/URPA nanoparticles on the drug resistance of MCF-7/ADR cells was perhaps related with their cell entry and intracellular drug release mechanisms. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:908 / 917
页数:10
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