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International Journal of Biomaterials
Volume 2013 (2013), Article ID 252531, 13 pages
http://dx.doi.org/10.1155/2013/252531
Research Article

Systemic siRNA Delivery via Peptide-Tagged Polymeric Nanoparticles, Targeting PLK1 Gene in a Mouse Xenograft Model of Colorectal Cancer

1Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Room 311, Lyman Duff Medical Building, Montreal, QC, Canada H3A 2B4
2Faculty of Dentistry, McGill University, 3775 University Street, Montreal, QC, Canada H3A 2B2

Received 17 June 2013; Accepted 7 August 2013

Academic Editor: Chwee Teck Lim

Copyright © 2013 Meenakshi Malhotra 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

Polymeric nanoparticles were developed from a series of chemical reactions using chitosan, polyethylene glycol, and a cell-targeting peptide (CP15). The nanoparticles were complexed with PLK1-siRNA. The optimal siRNA loading was achieved at an N : P ratio of 129.2 yielding a nanoparticle size of >200 nm. These nanoparticles were delivered intraperitoneally and tested for efficient delivery, cytotoxicity, and biodistribution in a mouse xenograft model of colorectal cancer. Both unmodified and modified chitosan nanoparticles showed enhanced accumulation at the tumor site. However, the modified chitosan nanoparticles showed considerably, less distribution in other organs. The relative gene expression as evaluated showed efficient delivery of PLK1-siRNA (0.5 mg/kg) with % knockdown ( ) of PLK1 gene. The in vivo data reveals no systemic toxicity in the animals, when tested for systemic inflammation and liver toxicity. These results indicate a potential of using peptide-tagged nanoparticles for systemic delivery of siRNA at the targeted tumor site.