title: Remote Control of Light-Triggered Virotherapy.
abstract: Clinical virotherapy has been successfully approved for use in cancer treatment by the U.S. Food and Drug Administration; however, a number of improvements are still sought to more broadly develop virotherapy. A particular challenge is to administer viral therapy systemically and overcome limitations in intratumoral injection, especially for complex tumors within sensitive organs. To achieve this, however, a technique is required that delivers the virus to the tumor before the body's natural self-defense eradicates the virus prematurely. Here we show that recombinant adeno-associated virus serotype 2 (AAV2) chemically conjugated with iron oxide nanoparticles (∼5 nm) has a remarkable ability to be remotely guided under a magnetic field. Transduction is achieved with microscale precision. Furthermore, a gene for production of the photosensitive protein KillerRed was introduced into the AAV2 genome to enable photodynamic therapy (PDT), or light-triggered virotherapy. In vivo experiments revealed that magnetic guidance of "ironized" AAV2-KillerRed injected by tail vein in conjunction with PDT significantly decreases the tumor growth via apoptosis. This proof-of-principle demonstrates guided and highly localized microscale, light-triggered virotherapy.
authors.affiliation: National Taiwan University Cancer Center (YongLin Scholar) , Taipei 10051, Taiwan.
authors.forename: S-Ja
authors.initials: SJ
authors.lastname: Tseng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Kuo-Yen
authors.initials: KY
authors.lastname: Huang
authors.affiliation: Future Industries Institute, University of South Australia , Mawson Lakes, S.A. 5095, Australia.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Kempson
authors.affiliation: Research Center for Tumor Medical Science, China Medical University , Taichung 40402, Taiwan.
authors.forename: Shih-Han
authors.initials: SH
authors.lastname: Kao
authors.affiliation: Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung 80424, Taiwan.
authors.forename: Meng-Chia
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Shuenn-Chen
authors.initials: SC
authors.lastname: Yang
authors.affiliation: Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung 80424, Taiwan.
authors.forename: Zi-Xian
authors.initials: ZX
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D000229:Dependovirus / Q000235:genetics*; D053758:Nanoparticles; D050130:Oncolytic Virotherapy; D010778:Photochemotherapy
keywords: adeno-associated virus; microtransduction; nanoparticle; photodynamic therapy; virotherapy