Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy

Title
Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy
Authors
이경근
Keywords
Cancer gene therapy; Oncolytic adenovirus; Magnetofection; PEGylated and cross-linked iron oxide nanoparticles; PCION
Issue Date
2015-07
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v. 65, Page. 163-174
Abstract
Adenovirus (Ad) is a widely used vector for cancer gene therapy but its therapeutic efficacy is limited by low coxsackievirus and adenovirus receptor (CAR) expression in tumors and non-specifically targeted infection. Ad infectivity and specificity can be markedly improved by creating Ad-magnetic nanoparticles cluster complexes and directing their migration with an external magnetic field (MGF). We electrostatically complexed GFP-expressing, replication-incompetent Ad (dAd) with PEGylated and cross-linked iron oxide nanoparticles (PCION), generating dAd-PCION complexes. The dAd-PCION showed increased transduction efficiency, independent of CAR expression, in the absence or presence of an MGF. Cancer cell killing and intracellular oncolytic Ad (HmT)-PCION replication significantly increased with MGF exposure. Site-directed, magnetically-targeted delivery of the HmT-PCION elicited significantly greater therapeutic efficacy versus treatment with naked HmT or HmT-PCION without MGF in CAR-negative MCF7 tumors. Immunohistochemical tumor analysis showed increased oncolytic Ad replication in tumors following infection by HmT-PCION using an MGF. Whole-body bioluminescence imaging of tumor-bearing mice showed a 450-fold increased tumor-to-liver ratio for HmT-PCION with, versus without, MGF. These results demonstrate the feasibility and potential of external MGF-responsive PCION-coated oncolytic Ads as smart hybrid vectors for cancer gene therapy. (C) 2015 Elsevier Ltd. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0142961215005773http://hdl.handle.net/20.500.11754/26142
ISSN
0142-9612; 1878-5905
DOI
http://dx.doi.org/10.1016/j.biomaterials.2015.07.001
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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