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Integrin Targeted Delivery of Gene Therapeutics

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Author(s): Rudy L Juliano, Xin Ming, Osamu Nakagawa, Rongzuo Xu, Hoon Yoo

Journal: Theranostics
ISSN 1838-7640

Volume: 1;
Issue: 1;
Start page: 211;
Date: 2011;
Original page

ABSTRACT
Integrins have become key targets for molecular imaging and for selective delivery of anti-cancer agents. Here we review recent work concerning the targeted delivery of antisense and siRNA oligonucleotides via integrins. A variety of approaches have been used to link oligonucleotides to ligands capable of binding integrins with high specificity and affinity. This includes direct chemical conjugation, incorporating oligonucleotides into lipoplexes, and use of various polymeric nanocarriers including dendrimers. The ligand-oligonucleotide conjugate or complex associates selectively with the integrin, followed by internalization into endosomes and trafficking through subcellular compartments. Escape of antisense or siRNA from the endosome to the cytosol and nucleus may come about through endogenous trafficking mechanisms, or because of membrane disrupting capabilities built into the conjugate or complex. Thus a variety of useful strategies are available for using integrins to enhance the pharmacological efficacy of therapeutic oligonucleotides.
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