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BioMed Research International
Volume 2013, Article ID 378380, 11 pages
http://dx.doi.org/10.1155/2013/378380
Research Article

Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery

1Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, 3710 McClintock Avenue, RTH509, Los Angeles, CA 90089, USA
2Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
3Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
4Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
5Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA

Received 26 December 2012; Revised 6 March 2013; Accepted 18 March 2013

Academic Editor: Claudete J. Valduga

Copyright © 2013 Yarong Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.