The development of novel therapeutic delivery methods is a major target in biotechnology and medicine, especially methods that reduce the therapeutic dosages required through site specific drug targeting. Protein cages derived from viral capsids, termed virus-like particles (VLPs), are of interest due to their ease of production, well characterized molecular assembly and architecture, and biocompatibility. The VLP derived from Escherichia coli bacteriophage HK97 is a potentially unique VLP platform for use in drug delivery applications due to its unique structural morphologies and reported selective cell entry properties. Experimental results have shown that HK97 VLP constructs penetrate the cell-membrane if they are externally engineered and decorated with the addition cell targeting peptides, such as the tripeptide Arg-Gly-Asp (RGDs), which mediates cell membrane binding. In order to determine the toxicity and localization of HK97 VLPs, zebra Danio (zebrafish) were used as an in vivo model system to examine the toxicity and localization of HK97 VLPs. Pilot studies suggested no significant difference of toxicity between fluorescently-labeled HK97 vs RGD-targeted fluorescently-labeled HK97- fluorescein when applied via soaking at 2 days post fertilization. Our work will confirm toxicity results and determine if RGD targeting limits VLP localization in a tissue specific manner.

Examination of the toxicity and localization of HK-97 virus-like particles in zebra Dario (zebrafish) for applications in drug delivery

ACS Spring 2022

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