Enzyme-responsive hydrogel particles for the controlled release of proteins: designing peptide actuators to match payload

We report on enzyme-responsive hydrogel particles for the controlled release of proteins. Amino-functionalised poly(ethylene glycol acrylamide) (PEGA) hydrogel particles were functionalised with peptide actuators that cause charge-induced swelling and payload release when triggered enzymatically. Peptide-based actuators were designed to match the specificity of the target enzyme, while also matching the charge properties of the to-be released protein payload, thereby uniquely allowing for tuneable release profiles. Fluorescently labelled albumin and avidin, proteins of similar size but opposite charge, were released at a rate that was governed by the peptide actuator linked to the polymer carrier, offering a highly controlled release mechanism. Release profiles were analysed using a combination of fluorescence spectroscopy of the solution and two-photon fluorescence microscopy to analyse enzymatically triggered molecular events within hydrogel particles during the initial stages of release.