Li Xiaoyu, Wu Meiying, Pan Limin, Shi Jianlin
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Int J Nanomedicine. 2015 Dec 29;11:93-105. doi: 10.2147/IJN.S81156. eCollection 2016.
To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4) and a chemotherapeutic drug (doxorubicin) and conjugate with targeting molecules (iRGD peptide) for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors.
为克服传统化疗中药物非选择性的缺点，构建多功能靶向药物递送系统是最有效且流行的方法之一。肿瘤内抗血管生成和杀伤肿瘤细胞是对抗肿瘤的两种基本方法。在此，我们报道了一种新型的肿瘤血管靶向多药递送系统，该系统使用介孔二氧化硅纳米颗粒作为载体，共负载抗血管生成剂（康普瑞汀A4）和化疗药物（阿霉素），并与靶向分子（iRGD肽）偶联，用于联合抗血管生成和化疗。这种双负载药物递送系统能够通过差异化的药物释放策略在肿瘤血管处递送这两种药物，然后在肿瘤内递送，因此在阿霉素剂量仅为1.5 mg/kg的极低剂量下，抗肿瘤疗效得到了极大提高。抗血管生成剂在肿瘤血管处的快速释放导致血管结构破坏，并与随后化疗药物缓慢释放到肿瘤中时的化疗药物产生协同作用。
