Near-Infrared-Triggered On-Demand Controlled Release of Adeno-Associated Virus from Alginate Hydrogel Microbeads with Heat Transducer for Gene Therapy |
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Authors: | Shuhei Takatsuka Takeshi Kubota Yuta Kurashina Hiroaki Onoe |
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Affiliation: | 1. Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223–8522 Japan;2. Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Hanamachi, Koganei-shi, Tokyo, 184–8588 Japan |
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Abstract: | Gene therapy using adeno-associated virus (AAV) has potential as a radical treatment modality for genetic diseases such as sensorineural deafness. To establish clinical applications, it is necessary to avoid immune response to AAV by controlled release system of AAV. Here, a near-infrared (NIR)-triggered on-demand AAV release system using alginate hydrogel microbeads with a heat transducer is proposed. By using a centrifuge-based microdroplet shooting device, the microbeads encapsulating AAV with Fe3O4 microparticles (Fe3O4-MPs) as a heat transducer are fabricated. Fe3O4-MPs generated heat by NIR enhanced the diffusion speed of the AAV, resulting in the AAV being released from the microbeads. By irradiating the microbeads encapsulating fluorescent polystyrene nanoparticles (FP-NPs) (viral model) with NIR, the fluorescence intensity decreased only for FP-NPs with a diameter of 20 nm and not for 100 or 200 nm, confirming that this system can release virus with a diameter of several tens of nanometers. By irradiating NIR to the AAV-encapsulating microbeads with Fe3O4-MPs, the AAV is released on demand, and gene transfection to cells by AAV is confirmed without loss of viral activity. The NIR-triggered AAV release system proposed in this study increases the number of alternatives for the method of drug release in gene therapy. |
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Keywords: | adeno-associated viruses (AAVs) alginate gene therapies hydrogel beads near-infrared on-demand DDS |
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