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Surface-Modified LPD Nanoparticles for Tumor Targeting

Authors

  • SHYH-DAR LI,

    1. Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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  • LEAF HUANG

    1. Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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Address for correspondence: Leaf Huang, Ph.D., CB 7360, 2316 Kerr Hall, Chapel Hill, NC 27599-7360. Voice: 919-843-0736; fax: 919-966-0197.
 e-mail: leafh@unc.edu

Abstract

Abstract: We have developed a tumor-targeted LPD formulation (liposome-polycation-DNA complex) for siRNA. With surface modification, the targeted, PEGylated LPD increased the delivery efficiency by four-fold and the gene-silencing effect by two- to three-fold. Downregulation of survivin in human lung cancer cells by targeted LPD induced 90% of apoptosis and sensitized the cells to cisplatin by four-fold. PEGylated LPD formulation also significantly improved the tumor localization of siRNA in the NCI-H460 human lung cancer xenograft model. The tumor appeared to be the major uptake organ for siRNA formulated in surface-modified LPD. Our encouraging results indicate that surface-modified LPD may be a potent carrier for RNAi-based tumor therapy.

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