Pan Yunlong, Ding Hui, Qin Li, Zhao Xiaoxu, Cai Jiye, Du Bin
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, P R China.
J Biomed Nanotechnol. 2013 Oct;9(10):1746-56. doi: 10.1166/jbn.2013.1678.
The inhibition of the binding between VEGFs and their receptors reduces angiogenesis and retards tumor growth. Owing to the large amount of antibodies required, the antibody-based anti-angiogenic drug remains limited. Gold nanoparticles (AuNPs) displayed excellent biocompatibility, low toxicity and anti-angiogenic effect, but the mechanism of anti-angiogenesis was unknown. Here, the antitumor effects of a well-dispersed AuNPs, specifically regarding its influence on VEGF signaling, were examined mechanistically. The effects of AuNPs on the interaction of VEGF with its receptor, VEGFR2 were observed using near-field scanning optical microscopy/quantum dot (NSOM/QD) imaging. We found AuNPs can reduce VEGF165-induced VEGFR2 and AKT phosphorylation. Furthermore, the antitumor effects of AuNPs were determined using xenograft and ascites model. AuNPs inhibited VEGF165-VEGFR2 interaction and suppressed the formation of nanodomains of VEGFR2 on the HUVEC. As determined by CD34 immunhistochemistry, AuNPs reduced angiogenesis in a liver tumor nude mice model, as observed by a decreased microvascular density in liver tumor sections and reduced the tumor weight and volume. In addition, AuNPs inhibited ascites formation in mice. Taken together, this study provides new insights into nanomaterial-based antitumor drug development.
抑制血管内皮生长因子（VEGFs）与其受体之间的结合可减少血管生成并延缓肿瘤生长。由于所需抗体量巨大，基于抗体的抗血管生成药物仍然受限。金纳米颗粒（AuNPs）具有出色的生物相容性、低毒性和抗血管生成作用，但其抗血管生成机制尚不清楚。在此，我们从机制上研究了一种分散良好的AuNPs的抗肿瘤作用，特别是其对VEGF信号传导的影响。使用近场扫描光学显微镜/量子点（NSOM/QD）成像观察了AuNPs对VEGF与其受体VEGFR2相互作用的影响。我们发现AuNPs可以降低VEGF165诱导的VEGFR2和AKT磷酸化。此外，使用异种移植和腹水模型确定了AuNPs的抗肿瘤作用。AuNPs抑制VEGF165-VEGFR2相互作用，并抑制人脐静脉内皮细胞（HUVEC）上VEGFR2纳米结构域的形成。通过CD34免疫组织化学测定，AuNPs可降低肝肿瘤裸鼠模型中的血管生成，如肝肿瘤切片中的微血管密度降低所示，并减轻肿瘤重量和体积。此外，AuNPs可抑制小鼠腹水形成。综上所述，本研究为基于纳米材料的抗肿瘤药物开发提供了新的见解。
