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ACS Nano. 2016 Nov 22;10(11):10339-10346. Epub 2016 Nov 7.

Remote Control of Light-Triggered Virotherapy.

Author information

1
National Taiwan University Cancer Center (YongLin Scholar) , Taipei 10051, Taiwan.
2
Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
3
Future Industries Institute, University of South Australia , Mawson Lakes, S.A. 5095, Australia.
4
Research Center for Tumor Medical Science, China Medical University , Taichung 40402, Taiwan.
5
Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung 80424, Taiwan.

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.

KEYWORDS:

adeno-associated virus; microtransduction; nanoparticle; photodynamic therapy; virotherapy

PMID:
27934080
DOI:
10.1021/acsnano.6b06051
[Indexed for MEDLINE]

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