Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy |
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| Affiliation: | 1. Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea;2. Graduated School, Dept. of Polymer Science & Engineering, SungKyunKwan University, Suwon 440-746, Republic of Korea;3. Department of Surgery, College of Medicine, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea;1. Departments of Dermatology, Pittsburgh, PA;2. Departments of Immunology, Pittsburgh, PA;3. Departments of Surgery, Pittsburgh, PA;4. Thomas E. Starzl Transplantation Institute, Pittsburgh, PA;5. University of Pittsburgh Cancer Institute, Pittsburgh, PA;6. McGowan Center for Regenerative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA;1. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Biochemistry, Higher Education Institute of Rab-Rashid, Tabriz, Iran;4. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;5. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China;2. College of Pharmaceutical Sciences, Soochow University, 199 RenAi Road, Suzhou Industrial Park, Suzhou City, Jiangsu Province 215123, China;1. Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA;2. Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland;3. Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), 70569 Stuttgart, Germany;4. Department of Chemical Engineering, Queen''s University, Kingston, ON, Canada;5. Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland;1. Key Laboratory of Zoonoses Research, Ministry of Education, Institute of Zoonosis, Department of Hepato-Biliary-Pancreatic Surgery, First Hospital, Jilin University, Changchun 130062, PR China;2. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China |
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| 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. |
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| Keywords: | Cancer gene therapy Oncolytic adenovirus Magnetofection PEGylated and cross-linked iron oxide nanoparticles (PCION) |
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