In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1516-1516
Abstract:
We are developing synthetic, engineered, ElectroNanoPlex™ nanoparticles for tumor targeted in vivo delivery of siRNA, plasmids, and other nucleic acids. These nanoparticles employ biodegradable cationic polyamide macromolecules that form an electrostatic association with the anionic nucleic acid cargo, and provide a hydrophilic steric polymer coating on the surface of the nanoparticles. Conditions have been identified to form siRNA or plasmid carrying nanoparticles with a mean diameter of approximately 100 nm, which falls within the range appropriate for enhanced permeability and retention (EPR) localization in tumor tissue. We have successfully delivered nucleic acids in vivo to solid tumors using nanoparticles with the steric coating but without a ligand for specific targeting, suggesting a mechanism of action based on EPR targeting. These nanoparticles are being commercialized under the tradename InVivoPlex™ for tumor gene function research, and drug target validation, in murine xenograft tumor models. Compared to other in vivo delivery technologies these nanoparticles show vastly diminished expression of plasmid DNA in lung, spleen, liver and kidney. Also, plasmid DNA and siRNA oligonucleotides can be co-packaged and delivered together using these nanoparticles, permitting studies of simultaneous down-regulation and up-regulation of different genes. Active targeting to cell surface receptors or antigens may be employed by decorating the nanoparticle surface with peptides such as cyclic RGD or monoclonal antibodies. Studies of antibody-mediated tumor cell delivery by ligand decorated nanoparticles will be presented. These nanoparticle systems will advance tumor targeted research using siRNA and are expected to eventually enable therapeutic applications of siRNA, or other nucleic acid agents that are promising in light of their molecular biological properties but currently face daunting pharmaceutical delivery challenges. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1516.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-1516
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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