Ai Shichao, Zhen Shuang, Liu Zhijian, Sun Feng, He Xingchen, Chu Feng, Guan Wenxian, Wang Jianquan
Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University Nanjing Jiangsu 210008 China
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University Nanjing China.
RSC Adv. 2018 Aug 24;8(52):30012-30020. doi: 10.1039/c8ra05071f. eCollection 2018 Aug 20.
The -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 and tumor tissues . Hence, we synthesized targeted nanoparticles iHP-DDP (iHDDP) and untargeted nanoparticles HP-DDP (HDDP). In our result, iHDDP showed higher antitumor efficacy than HDDP and . 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.
二氯二氨铂（II）（DDP，顺铂）是临床上治疗胃癌的一种重要抗肿瘤药物，但它受非特异性组织分布和严重副作用的限制。在此，成功合成了一种整合素靶向药物递送系统iRGD-肝素纳米载体（iHP）。iHP具有几个独特的特性。首先，由于其肝素生物聚合物框架，这种纳米载体具有优异的生物降解性。其次，它具有生物相容性，因为琥珀酸酐修饰的肝素没有抗凝活性和细胞毒性。我们通过抗凝功能评估和细胞毒性试验证明了这一点。第三，iRGD作为整合素靶向配体与纳米颗粒偶联。我们的结果表明，iHP对整合素过表达的人胃癌细胞MKN-45P和肿瘤组织具有精确靶向作用。因此，我们合成了靶向纳米颗粒iHP-DDP（iHDDP）和非靶向纳米颗粒HP-DDP（HDDP）。在我们的结果中，iHDDP显示出比HDDP更高的抗肿瘤疗效。并且与游离DDP相比，iHDDP纳米颗粒递送系统在携带MKN-45P肿瘤的裸鼠中显示出令人满意的DDP抗肿瘤活性，且无体重减轻或肝肾损伤。
