Journal
BIOMATERIALS
Volume 34, Issue 5, Pages 1613-1623Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.11.007
Keywords
Nanoparticle; Dendritic polymer; Self-assembly; Drug delivery; Antitumor; Biocompatibility
Funding
- National Basic Research Program of China (National 973 program) [2011CB606206]
- National Natural Science Foundation of China [51133004, 81101099, 50830105]
- International Collaboration Project of Ministry of Science Technology [2010DFA51550]
- International Cooperation Project of Sichuan Province [2009HH0001]
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Nanoparticles, such as dendritic polymers, are currently investigated as excellent candidates for drug delivery vehicles. In this study, we report the preparation and characterization of mPEGylated peptide dendron doxorubicin (dendron-DOX) conjugate based vehicle carrying 14.0 wt% (weight percent) of doxorubicin (DOX). Dynamic light scattering (DLS), scanning electron microscope (SEM) and transmission electron microscope (TEM) studies demonstrated the dendron DOX conjugate self-assembled into nanoscale particles with neutral charged surface. The globular morphology and compact nanoparticle with diameter around 80 nm were observed by SEM and TEM. The release rates of DOX from the nanoparticle at pH 5.0 were much faster than those at pH 7.4 due to the pH-sensitive cleavage of the hydrazone bonds. The nanoparticle was shown to effectively kill cancer cells in vitro. Importantly, the nanoparticle resulted in strong antitumor activity and induced apoptosis on the 4T1 breast tumor model. In vivo toxicity evaluation demonstrated that drug-free dendron and drug-loading nanoparticle provided good biosafety in healthy or tumor-bearing mice, because no significant systematic toxicity was revealed via histological analysis. The functionalized peptide dendron DOX conjugate based nanoparticle may be therefore a potential candidate for drug delivery vehicle for cancer therapy. (C) 2012 Elsevier Ltd. All rights reserved.
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