Recent advances in the tumor‐penetrating peptide internalizing RGD for cancer treatment and diagnosis

Abstract Cancer has become a prominent disease that seriously endangers human health. The complexity of the biological characteristics of the tumor makes it challenging for traditional therapeutic drugs to penetrate tumor tissues and exert their antitumor effects. Internalizing RGD peptide (iRGD) is a novel tumor‐homing peptide that binds to αvβ3 and αvβ5 integrins on the surface of tumor vessels through the C‐end rule (CendR) motif. The CendR motif binds to the neuropilin‐1 (NRP‐1) receptor on tumor cells, initiating NRP‐1‐mediated transcytosis to facilitate drug entry into the tumor tissue. Multiple studies demonstrated that iRGD improved the penetration and targeting of antitumor drugs, thereby enhancing their antitumor efficacy. In this review, we initially described the origins of iRGD and its penetration mechanism. Furthermore, we presented updates on the application of iRGD in cancer chemotherapy, photodynamic therapy, gene therapy, immunotherapy, treatment with antibodies or protein‐based biologics, and tumor imaging.