Matrix Metalloproteinase-Responsive Drug Delivery Systems

Matrix metalloproteinases (MMPs) are a class of endopeptidasesthat are dependent on zinc and facilitate the degradation of extracellularmatrix (ECM) proteins, thereby playing pivotal parts in human physiologyand pathology. MMPs regulate normal tissue and cellular functions,including tissue development, remodeling, angiogenesis, bone formation,and wound healing. Several diseases, including cancer, inflammation,cardiovascular diseases, and nervous system disorders, have been linkedto dysregulated expression of specific MMP subtypes, which can promotetumor progression, metastasis, and inflammation. Various MMP-responsivedrug delivery and release systems have been developed by harnessingcleavage activities and overexpression of MMPs in affected regions.Herein, we review the structure, substrates, and physiological andpathological functions of various MMPs and highlight the strategiesfor designing MMP-responsive nanoparticles to improve the targetingefficiency, penetration, and protection of therapeutic payloads.