iRGD peptide (c(CRGDKGPDC)) is a 9-amino acid cyclic peptide (sequence: CRGDKGPDC) and a molecular mimicry agent that was originally identified in an in vivo screening of phage display libraries in tumor-bearing mice.

iRGD peptide-mediated tumor penetration involves a three-step process: initial binding to αv-integrins present on tumor vasculature or cells, the revelation of a C-terminal motif capable of binding to neuropilin-1 (NRP-1) through proteolysis, and subsequent cell internalization. Incorporation of the iRGD peptide into the ICOVIR15K fiber's C terminus specifically improves binding and internalization in MCF7 cells, known to express NRP-1 and integrins, without affecting the virus's ability to infect and replicate[1]. Alone, the iRGD peptide does not significantly impact gastric cancer cells. However, when combined with 5-FU, it notably enhances the chemotherapy's efficacy against gastric cancer cells via NRP1, at a concentration of 0.3 μmol/mL[2].

iRGD inserted in the oncolytic adenovirus ICOVIR15K (ICOVIR15K-iRGD) enhances early adenovirus dissemination through the tumor mass and elevates the antitumor effect in mice[1]. In vivo, iRGD did not change the normal organ transduction pattern, with liver and spleen as main targeted organs. iRGD (4 mmol/kg, i.v.) in combination with 5-FU significantly suppresses the tumor growth in nude mice bearing human gastric cancer cells[2].