Gong Xiaojin, Zhao Qian, Song Mu, Xue Feng
Department of Pathology, Second Affiliated Hospital, Xinjiang Medical University, Urumqi, 830063, China.
Department of Breast Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, 830011, China.
J Nanosci Nanotechnol. 2018 Apr 1;18(4):2379-2386. doi: 10.1166/jnn.2018.14541.
In our study, we report on the design and characterization of a combined angiogenesis therapy for breast cancer based on well-formed amine-functionalized silica nanoparticles (SLNs). The aminefunctionalized SLNs was employed to simultaneously deliver angiostatin (ANG) plasmid and candesartan (CD) to the same cancer cell. The well-formed ANG/CD/SLNs exhibited small particle size, reasonable positive charges, excellent loading of drug and gene in vitro. Moreover, aminefunctionalized SLNs were almost no cytotoxicity. ANG/CD/SLNs resulted in enhanced gene transfection compared to naked plasmid. More importantly, ANG/CD/SLNs as a co-delivery system achieved a stronger inhibitory effect on angiogenesis in vitro, possibly resulting from significant downregulation of vascular endothelial growth factor (VEGF) expression via different pathways. In particular, in vivo investigation on nude mice bearing MCF-7 xenografts confirmed that ANG/CD/SLNs codelivery system exerted strong anti-tumor efficacy by synergistic antiangiogenic mechanism.
在我们的研究中，我们报道了基于形态良好的胺功能化二氧化硅纳米颗粒（SLNs）的乳腺癌联合血管生成疗法的设计与特性。胺功能化的SLNs被用于同时将血管抑素（ANG）质粒和坎地沙坦（CD）递送至同一癌细胞。形态良好的ANG/CD/SLNs呈现出小粒径、合理的正电荷、体外优异的药物和基因负载量。此外，胺功能化的SLNs几乎没有细胞毒性。与裸质粒相比，ANG/CD/SLNs导致基因转染增强。更重要的是，ANG/CD/SLNs作为一种共递送系统在体外对血管生成具有更强的抑制作用，这可能是由于通过不同途径显著下调血管内皮生长因子（VEGF）表达所致。特别地，对携带MCF-7异种移植瘤的裸鼠进行的体内研究证实，ANG/CD/SLNs共递送系统通过协同抗血管生成机制发挥了强大的抗肿瘤功效。
