Step 2, the enzymatically cleavable linkers (matrix metalloproteinase 2 [MMP-2] responsive peptides) that are attached to the cell penetration-enhancing R8 peptide in the middle shell ensure the glioblastoma cell internalization following MMP-2 cleavage in the tumor microenvironment (Cui et al., 2016). The gene discussed is MMP2; the disease is neoplasm.