Near‐Infrared‐Triggered On‐Demand Controlled Release of Adeno‐Associated Virus from Alginate Hydrogel Microbeads with Heat Transducer for Gene Therapy

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 Fe 3 O 4 microparticles (Fe 3 O 4 ‐MPs) as a heat transducer are fabricated. Fe 3 O 4 ‐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 Fe 3 O 4 ‐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.