(601f) Viral Particle Release from Smart Hydrogel Scaffolds

^{b Department of NanoEngineering, University of California-San Diego, La Jolla, CA 92039, USA}

^{c Department of Radiology, University of California-San Diego, La Jolla, CA 92039, USA}

^{d Moores Cancer Center, University of California-San Diego, La Jolla, CA 92039, USA}

^{e Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, CA 92039, USA}

^{f Institute for Materials Discovery and Design, University of California-San Diego, La Jolla, CA 92039, USA}

Stimuli-responsive hydrogels, also dubbed smart hydrogels, have been the subject of intense research for drug delivery purposes. External or environmental factors enable delivery of target molecules with temporal and spatial control. In particular, temporal and repeated delivery of biomolecules can alleviate the need for repeated drug administration and therefore increase patience compliance.

A new class of therapeutics are plant virus-based drug delivery carriers, vaccines, and immunotherapies. Plant viruses can be manufactured in their natural host plants at high yield and offer durable thermal stability over a wide temperature range, hence could be stored and shipped at room temperature. Also, nanoparticles from plant viruses or their virus-like particles (VLPs) are biocompatible, biodegradable and offer chemical versatility. Plant viruses are non-infectious toward mammals.

In this work, the VLPs from Physalis mottle virus (PhMV) were used as a model system to create smart hydrogels for delivery of viral payloads. 30 nm-sized VLPs were produced through recombinant expression in Escherichia coli. The high valency of these particles – 720 surface-exposed lysine residues per VLP – allows for multivalent display of chemical handles to induce polymerization upon introduction of appropriate linkers. Using a combination of materials, we have prepared a virus-laden hydrogels to be used as depots for sustained virus delivery – the degradation rates are tuned through choice of chemistry and thus can be tailored for desired applications.

Acknowledgments: This work was supported by the NSF Center for the Chemistry of Molecularly Optimized Networks (MONET), CHE-2116298.

COI: Dr. Steinmetz is a co-founder of, has equity in, and has a financial interest with Mosaic ImmunoEngineering Inc. Dr. Steinmetz serves as Director, Board Member, and Acting Chief Scientific Officer, and paid consultant to Mosaic.