Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy
- Authors
- Choi, Joung-Woo; Park, Ji Won; Na, Youjin; Jung, Soo-Jung; Hwang, June Kyu; Choi, Dongho; Lee, Kyeong Geun; Yun, Chae-Ok
- Issue Date
- Oct-2015
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Cancer gene therapy; Oncolytic adenovirus; Magnetofection; PEGylated and cross-linked iron oxide nanoparticles (PCION)
- Citation
- BIOMATERIALS, v.65, pp.163 - 174
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 65
- Start Page
- 163
- End Page
- 174
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24839
- DOI
- 10.1016/j.biomaterials.2015.07.001
- ISSN
- 0142-9612
- 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.
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