Inhibitory effects of trolox-encapsulated chitosan nanoparticles on tert-butylhydroperoxide induced RAW264.7 apoptosis

被引:50
作者
Han, Lu [1 ]
Du, Li-Bo [1 ]
Kumar, Anil [2 ]
Jia, Hong-Ying [1 ]
Liang, Xing-Jie [2 ]
Tian, Qiu [1 ]
Nie, Guang-Jun [2 ]
Liu, Yang [1 ]
机构
[1] Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100190, Peoples R China
[2] Chinese Acad Sci, Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
基金
中国国家自然科学基金;
关键词
Trolox; Chitosan nanoparticles; Anti-Oxidation activities; Anti-Apoptosis effects; POLYMERIC MICELLES; IN-VITRO; ANTIOXIDANT; DELIVERY; BIOAVAILABILITY; CHITIN; DEATH;
D O I
10.1016/j.biomaterials.2012.07.034
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
A nanocarrier, namely, hydroxylethyl-chitosan nanoparticles was developed in this research for delivering antioxidants with 6-hydroxy-2, 5, 7, 8-tetra-methylchromane-2-carboxylic acid (trolox) as a model antioxidant. The trolox-encapsulated chitosan nanoparticles (trolox-CS NPs) were prepared by modifying chitosan with epoxyethane, which self-assembled into NPs and entrapped trolox, and then characterized by their size, size distribution, morphology and in vitro trolox release profile. Intracellular trafficking of CS NPs was observed. The anti-oxidant effect and potential mechanism of trolox-CS NPs were subsequently investigated in RAW264.7 cells. The effects of trolox-CS NPs on RAW264.7 cells damaged by tert-butylhydroperoxide (t-BHP) were determined by MTT assay for cell viability, MDA assay for membrane lipid peroxidation, JC-1 probe and Annexin V-FITC/PI double staining for mitochondria membrane potential (MMP) and RAW264.7 apoptosis, respectively. The trolox-CS NPs significantly improved cell viability and reduced MDA content compared with those of cells treated with free trolox. The trolox-CS NPs treatment inhibited MMP collapse and RAW264.7 apoptosis more obviously than free trolox. Molecular basis of apoptosis studied by western blotting revealed that trolox-CS NPs may block mitochondria-mediated apoptosis pathway through up-regulation of Bcl-2 and down-regulation of Bax and inhibiting the activation of pro-caspase 3, PARP and Bid. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:8517 / 8528
页数:12
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