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pubmed-article:16807119pubmed:abstractTextThe present studies investigated the hypothesis that affinity immobilization of replication-defective adenoviruses (Ad) on the surfaces of biodegradable nanoparticles (NP) can improve transduction through uncoupling cellular uptake from the coxsackie-adenovirus receptor (CAR). Ad was tethered to the surfaces of polylactide-based NP that were surface-activated using a photoreactive polyallylamine-benzophenone-pyridyldithiocarboxylate polymer, which enabled (via thiol chemistry) the covalent attachment of Ad-binding proteins, either the recombinant D1 domain of CAR or an adenoviral knob-specific monoclonal antibody. Gene transfer by NP-Ad complexes was studied in relation to cellular uptake as a function of cell type and the character of NP-Ad binding. NP-Ad complexes, but not Ad applied with or without control nonimmune IgG-modified NP, significantly increased green fluorescent protein reporter expression in endothelioma and endothelial and arterial smooth muscle cells (SMC) in direct correlation to the extent of NP-Ad internalization. CAR-independent uptake of NP-Ad was confirmed by demonstrating inhibition of free Ad- but not NP-Ad complex-mediated transduction by knob protein. Complexes formulated with an Ad encoding inducible nitric oxide synthase inhibited growth of cultured SMC to a significantly greater extent than those with (GFP)Ad or (NULL)Ad or free vector. It is concluded that Ad-specific affinity tethering to biodegradable NP can significantly increase the level of gene expression via a CAR-independent uptake mechanism.lld:pubmed
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pubmed-article:16807119pubmed:articleTitleAdenoviral gene vector tethering to nanoparticle surfaces results in receptor-independent cell entry and increased transgene expression.lld:pubmed
pubmed-article:16807119pubmed:affiliationDivision of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.lld:pubmed
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pubmed-article:16807119pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:16807119pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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