Intratracheal administration of a nanoparticle-based therapy with the angiotensin II type 2 receptor gene attenuates lung cancer growth

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dc.contributor.author Kawabata, Atsushi
dc.contributor.author Baoum, Abdulgader
dc.contributor.author Ohta, Naomi
dc.contributor.author Jacquez, Stephanie
dc.contributor.author Seo, Gwi-Moon
dc.contributor.author Berkland, Cory
dc.contributor.author Tamura, Masaaki
dc.date.accessioned 2012-11-06T19:38:15Z
dc.date.available 2012-11-06T19:38:15Z
dc.date.issued 2012-11-06
dc.identifier.uri http://hdl.handle.net/2097/14901
dc.description.abstract Targeted gene delivery, transfection efficiency and toxicity concerns remain a challenge for effective gene therapy. In this study, we dimerized the HIV-1 TAT peptide and formulated a nanoparticle vector (dTAT NP) to leverage the efficiency of this cell penetrating strategy for tumor-targeted gene delivery in the setting of intratracheal administration. Expression efficiency for dTAT NP-encapsulated luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) was evaluated in Lewis Lung carcinoma (LLC) cells cultured in vitro or in vivo in orthotopic tumor grafts in syngeneic mice. In cell culture, dTAT NP was an effective pDNA transfection vector with negligible cytotoxicity. Transfection efficiency was further increased by addition of calcium and glucose to dTAT/pDNA NP. In orthotopic tumor grafts, immunohistochemical analysis confirmed that dTAT NP successfully delivered pDNA to the tumor, where it was expressed primarily in tumor cells along with the bronchial epithelium. Notably, gene expression in tumor tissues persisted at least 14 days after intratracheal administration. Moreover, bolus administration of dTAT NP-encapsulated AT2R or TRAIL pDNA markedly attenuated tumor growth. Taken together, our findings offer a preclinical proof of concept for a novel gene delivery system that offers an effective strategy for locally administering lung cancer gene therapy. en_US
dc.language.iso en_US en_US
dc.relation.uri http://cancerres.aacrjournals.org/content/72/8/2057 en_US
dc.subject Angiotensin II type 2 receptor en_US
dc.subject Cationic peptide nanoparticles en_US
dc.subject Lung adenocarcinoma en_US
dc.subject Targeted gene therapy en_US
dc.subject Apoptosis en_US
dc.subject Transfection en_US
dc.title Intratracheal administration of a nanoparticle-based therapy with the angiotensin II type 2 receptor gene attenuates lung cancer growth en_US
dc.type Article (author version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1158/0008-5472.CAN-11-3634 en_US
dc.citation.epage 2067 en_US
dc.citation.issue 8 en_US
dc.citation.jtitle Cancer Research en_US
dc.citation.spage 2057 en_US
dc.citation.volume 72 en_US
dc.contributor.authoreid masaakit en_US

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