An iRGD peptide conjugated heparin nanocarrier for gastric cancer therapy

The cis-diamminedichloroplatinum(ii) (DDP, cisplatin) is an important antitumor drug for the therapy of gastric cancer in clinics, but it is limited by its nonspecific tissue distribution and severe side effects. Here, an integrin targeted drug delivery system iRGD-heparin nanocarrier (iHP) was successfully synthesized. The iHP has several unique properties. First, this nanocarrier has excellent biodegradation due to its heparin biopolymer frame. Second, it is biocompatible because succinic anhydride-modified heparin has no anticoagulant activity and cell toxicity. We proved that from anticoagulant function evaluation and a cytotoxicity test. Third, iRGD was conjugated to the nanoparticles as an integrin-targeting ligand. Our results showed that iHP has precise targeting to integrin-overexpressed human gastric cancer cells MKN-45P in vitro and tumor tissues in vivo. Hence, we synthesized targeted nanoparticles iHP-DDP (iHDDP) and untargeted nanoparticles HP-DDP (HDDP). In our result, iHDDP showed higher antitumor efficacy than HDDP in vitro and in vivo. And in comparison with free DDP, the iHDDP nanoparticle delivery system showed satisfactory antitumor activity of DDP without weight loss or liver and kidney damage in nude mice bearing MKN-45P tumors.