Besides tumor acidity, enzymes that are overexpressed in malignant tissues have also been frequently utilized to trigger shielding/deshielding transitions.500–502 For instance, to prevent non-specific cellular uptake of cell-penetrating peptides (CPP) in circulation, they were covalently attached to pH-sensitive masking peptides via the MMP-2 cleavable linker PLGLAG.500,501 The masking peptide is negatively charged and can effectively shield the cationic CPP from non-cancerous cells in normal physiological pH conditions. The gene discussed is MMP2; the disease is neoplasm.