Document Detail

Activatable Cell Penetrating Peptide-Conjugated Nanoparticles with Enhanced Permeability for Site-Specific Targeting Delivery of Anticancer Drug.
MedLine Citation:
PMID:  23350619     Owner:  NLM     Status:  Publisher    
Based on the powerful cell-penetrating ability of low molecular weight protamine (LMWP) and the over-expression of matrix metalloproteinases in the tumor sites, we here constructed an activatable low molecular weight protamine (ALMWP) and modified it onto the surface of PEG-PLA nanoparticles to develop a 'smart' drug delivery system with enhanced permeability for facilitating site-specific targeting delivery of anticancer drug. The obtained ALMWP-NP with a particle size of 134.0 ± 4.59 nm and a zeta potential of -34.4 ± 2.7 mV, exhibited an enhanced MMP-dependent accumulation in HT-1080 cells via both energy-independent direct translocation and clathrin-mediated, cytoskeleton-dependent endocytosis. Pharmacokinetic and biodistribution study in HT-1080 tumor-bearing mice showed that ALMWP-NP significantly increased the accumulation of paclitaxel (PTX) in the tumor site but not the non-target tissues. In addition, intra-tumor distribution analysis demonstrated that more ALMWP-NP penetrated deeply into the tumor parenchyma. As a result, PTX loaded by ALMWP-NP exhibited improved anti-tumor efficacy over that by NP and LMWP-NP. The findings suggested that ALMWP-NP could be used as a safe and effective tumor-targeting drug delivery system and opened a new gateway to the application of cell-penetrating peptides for targeted anti-tumor therapy.
Huimin Xia; Guangzhi Gu; Quanyin Hu; Zhongyang Liu; Mengyin Jiang; Ting Kang; Deyu Miao; Qingxiang Song; Lei Yao; Yifan Tu; Hongzhuan Chen; Xiaoling Gao; Jun Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-28
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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