NRP1 and neoplasm: The iRGD peptide has a three-step tumor targeting mechanism: (1) the iRGD peptide binds to αvβ3 and αvβ5 integrins, but not to α5β1 integrin, on the tumor endothelium through the RGD motif; (2) the peptide is proteolytically cleaved to produce CRGDK/R and expose a C-end rule (CendR) motif (R/KXXR/K) within the TME; (3) the CendR motif binds to neuropilin-1 and -2 (NRP-1/2) upon activation to trigger tumor tissue penetration [146].