TY - JOUR
T1 - Inhibitory effects of trolox-encapsulated chitosan nanoparticles on tert-butylhydroperoxide induced RAW264.7 apoptosis
AU - Han, Lu
AU - Du, Li Bo
AU - Kumar, Anil
AU - Jia, Hong Ying
AU - Liang, Xing Jie
AU - Tian, Qiu
AU - Nie, Guang Jun
AU - Liu, Yang
N1 - Funding Information:
This work was financially supported in part by grants from the National Natural Science Foundation of China (No. 90813021 and 21005082 ), and Knowledge Innovation Program (No. KJCX2-EW-H01 ) of Chinese Academy of Sciences .
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - Anti-Apoptosis effects
KW - Anti-Oxidation activities
KW - Chitosan nanoparticles
KW - Trolox
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U2 - 10.1016/j.biomaterials.2012.07.034
DO - 10.1016/j.biomaterials.2012.07.034
M3 - Article
C2 - 22922024
AN - SCOPUS:84866182280
SN - 0142-9612
VL - 33
SP - 8517
EP - 8528
JO - Biomaterials
JF - Biomaterials
IS - 33
ER -