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A redox-sensitive and RAGE-targeting nanocarrier for hepatocellular carcinoma therapy
Fang X.-B.3; Xu Y.-Q.3; Chan H.-F.2; Wang C.-M.3; Zheng Q.1; Xiao F.1; Chen M.-W.3
2016-11-07
Source PublicationMolecular Pharmaceutics
ISSN15438392 15438384
Volume13Issue:11Pages:3613-3625
Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells. Specifically, we modified Pluronic F68 (F68) with APDTKTQ (F68-APDTKTQ), and we conjugated d-α-tocopheryl polyethylene glycol succinate (TPGS) with poly(lactic-co-glycolic acid) (PLGA) by a disulfide linker (TPGS-S-S-PLGA). We mixed TPGS-S-S-PLGA and F68-APDTKTQ (TSP/FP) to form a micelle, followed by the loading of oridonin (ORI). The prepared micelles showed a homogeneously spherical shape without aggregation, triggered an increased cellular uptake, and induced apoptosis in more cells than did the free ORI. Taken together, these results demonstrate the potential of this APDTKTQ-modified ORI-loaded TSP/FP mixed micelle system as a promising strategy for HCC-targeting therapy.

KeywordHcc Oridonin Pluronic F68 Rage Redox-sensitivity
DOI10.1021/acs.molpharmaceut.6b00116
URLView the original
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000387428300002
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Jinan University
2.Columbia University in the City of New York
3.University of Macau
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Fang X.-B.,Xu Y.-Q.,Chan H.-F.,et al. A redox-sensitive and RAGE-targeting nanocarrier for hepatocellular carcinoma therapy[J]. Molecular Pharmaceutics,2016,13(11):3613-3625.
APA Fang X.-B..,Xu Y.-Q..,Chan H.-F..,Wang C.-M..,Zheng Q..,...&Chen M.-W..(2016).A redox-sensitive and RAGE-targeting nanocarrier for hepatocellular carcinoma therapy.Molecular Pharmaceutics,13(11),3613-3625.
MLA Fang X.-B.,et al."A redox-sensitive and RAGE-targeting nanocarrier for hepatocellular carcinoma therapy".Molecular Pharmaceutics 13.11(2016):3613-3625.
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