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Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment
Chen F.; Zhang J.; Wang L.; Wang Y.; Chen M.
2015
Source PublicationNanoscale
ISSN20403364
Volume7Issue:38Pages:15763
Abstract

The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ≈ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 ± 2.5 mV to +22.5 ± 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy. © The Royal Society of Chemistry 2015.

DOIhttp://doi.org/10.1039/c5nr04612b
URLView the original
Indexed BySCI
Language英语
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied
WOS IDWOS:000361834100028
The Source to ArticleScopus
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Cited Times [WOS]:40   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang Y.; Chen M.
AffiliationState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Chen F.,Zhang J.,Wang L.,et al. Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment[J]. Nanoscale,2015,7(38):15763.
APA Chen F.,Zhang J.,Wang L.,Wang Y.,&Chen M..(2015).Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment.Nanoscale,7(38),15763.
MLA Chen F.,et al."Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment".Nanoscale 7.38(2015):15763.
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