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.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Joung-Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Graduated School, Dept. of Polymer Science & Engineering, SungKyunKwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Na
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: June Kyu
authors.initials: JK
authors.lastname: Hwang
authors.affiliation: Department of Surgery, College of Medicine, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Dongho
authors.initials: D
authors.lastname: Choi
authors.affiliation: Department of Surgery, College of Medicine, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
authors.forename: Kyeong Geun
authors.initials: KG
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea. Electronic address: chaeok@hanyang.ac.kr.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
mesh_terms: D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry*; D015316:Genetic Therapy; D006801:Humans; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000737:chemistry* / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D014161:Transduction, Genetic
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols
keywords: Cancer gene therapy; Magnetofection; Oncolytic adenovirus; PEGylated and cross-linked iron oxide nanoparticles (PCION)