MMP-Responsive ‘Smart’ Drug Delivery and Tumor Targeting

Matrix metalloproteinases (MMPs) are major extracellular enzymes involved in cancer initiation, progression, and metastasis. MMPs are widely used as cancer biomarkers and therapeutic targets. Recently, MMPs have been investigated as robust tumor microenvironmental stimuli for 'smart' MMP-responsive drug delivery and tumor targeting and have shown great potential in cancer diagnosis and therapy. In this article, we review the newly emerging MMP-responsive strategies and major MMP-responsive nanomaterials and nanocarriers used for tumor-targeted delivery of drugs and imaging agents at the tissue, cellular, and intracellular levels. We also discuss the challenges and critical considerations in their development and clinical translation.