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

• Published in: Biomaterials Vol. 65; pp. 163 - 174
• Main Authors: Choi, Joung-Woo, Park, Ji Won, Na, Youjin, Jung, Soo-Jung, Hwang, June Kyu, Choi, Dongho, Lee, Kyeong Geun, Yun, Chae-Ok
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2015
• Subjects: Adenoviridae - chemistry; Adenoviridae - genetics; Advanced Basic Science; Animals; Cancer gene therapy; Cell Line, Tumor; Dentistry; Ferric Compounds - chemistry; Genetic Therapy; Humans; Magnetic Fields; Magnetite Nanoparticles - chemistry; Magnetofection; Mice; Neoplasms - genetics; Neoplasms - therapy; Oncolytic adenovirus; Oncolytic Virotherapy - methods; Oncolytic Viruses - chemistry; Oncolytic Viruses - genetics; PEGylated and cross-linked iron oxide nanoparticles (PCION); Polyethylene Glycols - chemistry; Transduction, Genetic; PEGylated and cross-linked iron oxide nanoparticles (PCION); Magnetofection; Cancer gene therapy; Oncolytic adenovirus
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.07.001

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.