Extracellular Matrix Component Shelled Nanoparticles as Dual Enzyme-Responsive Drug Delivery Vehicles for Cancer Therapy

Stimuli-responsive drug delivery systems with reduced side effects offer promising prospects for cancer therapy. In this study, we developed an enzyme-responsive nanomedicine system based on extracellular matrix components (ECM) shelled mesoporous silica nanoparticles. The covalently conjugated ECM biomacromolecules, hyaluronic acid and collagen I, can not only enhance the biocompatibility of the particles and avoid early drug leakage, but also allow selective biodegradation triggered by hyaluronidase (HAase) and Matrix metalloproteinases 2 (MMP-2), which are overexpressed enzymes in some tumor tissues. The in vitro cytotoxicity test confirmed favorable biocompatibility of the as-prepared nanomedicine system. Moreover, this system showed distinguishing controlled release efficiency toward cancer cells induced by different levels of HAase and MMP-2. The in vivo antitumor test demonstrated the excellent efficiency of our system for tumor targeting drug delivery and tumor growth inhibition. Therefore, this dual enzyme-responsive drug delivery system provided an efficient platform for cancer therapy.