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Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability
Guo, Zhaopei; Zhou, Xingzhi; Xu, Mengze; Tian, Huayu; Chen, Xuesi; Chen, Meiwan
2017-12
Source PublicationBIOMATERIALS SCIENCE
ISSN2047-4830
Volume5Issue:12Pages:2501-2510
AbstractCamptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ecarbobenzoxy- L-lysine (epsilon-Lys(Z)) and L-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide. DCPT was synthesized by reacting CPT and 2-hydroxyethyl disulfide, and micelles were prepared using a dialysis method. The obtained DCPT-loaded RGD-PEG-g-poly-L-lysine-b-poly-L-leucine (DRPPP) micelles showed a high encapsulation efficiency of 89.7% and a high drug loading capacity of 46.1%. In addition, the DRPPP micelles remained stable under physiological conditions (PBS at a pH of 7.4) but showed rapid release when triggered by a reductive environment (PBS at a pH of 7.4 with 10 mM dithiothreitol). Compared to micelles without RGD decoration, the DRPPP micelles exhibited an increased cellular uptake through RGD targeting and were internalized into cells via caveolae-mediated endocytosis and macropinocytosis. Furthermore, the DRPPP micelles exerted an enhanced cytotoxicity against MDA-MB-231 cells compared to MCF-7 cells, which expressed less alpha(v)beta(3) receptors. Besides, the DRPPP micelles induced cell apoptosis and caused a decrease of mitochondrial membrane potential. These results indicate that dimeric camptothecin-loaded cationic polypeptide-based micelle is a promising strategy for cancer therapy.
DOI10.1039/c7bm00791d
URLView the original
Indexed BySCI
Language英语
WOS Research AreaMaterials Science
WOS SubjectMaterials Science, Biomaterials
WOS IDWOS:000415872900015
PublisherROYAL SOC CHEMISTRY
The Source to ArticleWOS
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Guo, Zhaopei,Zhou, Xingzhi,Xu, Mengze,et al. Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability[J]. BIOMATERIALS SCIENCE,2017,5(12):2501-2510.
APA Guo, Zhaopei,Zhou, Xingzhi,Xu, Mengze,Tian, Huayu,Chen, Xuesi,&Chen, Meiwan.(2017).Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability.BIOMATERIALS SCIENCE,5(12),2501-2510.
MLA Guo, Zhaopei,et al."Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability".BIOMATERIALS SCIENCE 5.12(2017):2501-2510.
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