QCM-D assay for quantifying the swelling, biodegradation, and protein adsorption of intelligent nanogels

Environmentally responsive nanomaterials have been developed for drug delivery applications, in an effort to target and accumulate therapeutic agents at sites of disease. Within a biological system, these nanomaterials will experience diverse conditions which encompass a variety of solute identities and concentrations. In this study, we developed a new quartz crystal microbalance with dissipation (QCM-D) assay, which enabled the quantitative analysis of nanogel swelling, protein adsorption, and biodegradation in a single experiment. As a proof of concept, we employed this assay to characterize non-degradable and biodegradable poly(acrylamide-co-methacrylic acid) nanogels. We compared the QCM-D results to those obtained by dynamic light scattering to highlight the advantages and limitations of each method. We detailed our protocol development and practical recommendations, and hope that this study will serve as a guide for others to design application-specific QCM-D assays within the nanomedicine domain.