Matrix metalloproteinase inhibitors (MMPIs) as attractive therapeutic targets: Recent progress and current challenges

Abstract Matrix metalloproteinase (MMP) plays an essential role in many physiological and pathological processes. An increase in MMP activity contributes to excessive degradation and remodeling of the extracellular matrix (ECM), which has been correlated with invasion and metastasis of tumors. Matrix metalloproteinase inhibitor (MMPI) has been developed as an attractive therapeutic target for decades, suggesting inspiring therapeutic effects in preclinical studies. However, achieving specificity remains an important challenge in the development of MMPIs, limiting their clinical application and bringing about the risk of biosafety. Nanomaterials can be used as alternative candidates for MMPI design, providing a new strategy for this problem. This report reviewed the research about MMPIs, summarized their MMPs activity regulation mechanisms, and discussed their failures in clinical trials. Furthermore, we outlined several schemes of MMPIs screening and design. Finally, we reviewed the therapeutic application prospects of MMPIs and discussed the remaining challenges and solutions, which may offer new insights for the development of MMPIs studies.