Abstract
The wide array of proteases, including matrix metalloproteinases, produced in response to many pathogenic insults, confers a unique proteolytic signature which is often disease specific and provides a potential therapeutic target for drug delivery. Here we propose the use of collagen-based nanoenhanced matrix metalloproteinase-responsive delivery vehicles that display matrix metalloproteinase-specific degradation in diverse in vitro models of proteolysis. We demonstrate that collagen particles comprised of protease substrates (primarily collagen) can be made of uniform size and loaded efficiently with assorted cargo including fluorescently labeled mesoporous silica, magnetic nanoparticles, proteins and antioxidants. We also demonstrate that pathologic concentrations of proteases produced in situ or in vitro display protease-specific cargo release. Additionally, we show that the collagen-based particles display bright fluorescence when loaded with a fluorophore, and have the potential to be used as vehicles for targeted delivery of drugs or imaging agents to regions of high proteolytic activity.