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

Paper ID Volume ID Publish Year Pages File Format Full-Text
5600 405 2015 12 PDF Available
Title
Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy
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.

Keywords
Cancer gene therapy; Oncolytic adenovirus; Magnetofection; PEGylated and cross-linked iron oxide nanoparticles (PCION)
First Page Preview
Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 65, October 2015, Pages 163–174
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering