A simple swell-and-click method for the covalent attachment of virus-like particles to polymer hydrogels

Plant virus-like particles (VLPs) are biocompatible, non-infectious nanomaterials with promising applications as immunotherapeutics and vaccines. However, slow-release VLP formulations are needed to achieve long-term efficacy without repeated administration. VLP hydrogels allow the encapsulation and sustained delivery of VLPs, but the particles must covalently bind the hydrogel polymers to avoid premature loss. This has been achieved so far by in situ VLP polymerization, which requires high viral concentrations (5–10 mg/mL, 0.5–1 wt%) to form stable hybrid VLP–hydrogel networks and this complicates scalability and clinical translation. Here, we developed a novel swell-and-click method that led to successful VLP scaffold formation regardless of the viral load used. As a result, VLP-functionalized hydrogels were fabricated with viral concentrations as low as 0.1–1 mg/mL (0.01–0.1 % wt%) without compromising the scaffold stability on the process. The hydrogels incorporate VLPs during swelling, followed by copper-free click chemistry reactions that bind the particles covalently to the polymer. The swell-and-click method also resulted in more than a two-fold enhancement in VLP uptake into the hydrogels and it provides a means of combined burst release and prolonged sustained release, desired traits for cancer immunotherapy treatment. The present work introduces a novel methodology for the design of VLP-based hydrogels, which could facilitate the scalability of the fabrication process and move a significant step forward towards clinical translation of long-term VLP vaccination in cancer disease.

Duke Scholars

Author Stephen L Craig Chemistry