Pathological angiogenesis is driven by uncontrolled growth of endothelial cells (ECs), which could lead to retinopathy, tumor and rheumatoid arthritis, etc. ECs must experience multiple cell division process to grow, and cytokinesis is the final step. The present study shows that PEGylated GNRs (PEG-GNRs) specifically target ECs cytokinesis process which results in high ratio of binucleated cells, and these binucleated ECs lose the ability to proliferate. Further data show that PEG-GNRs do not induce toxicity in vitro and in vivo. PEG-GNRs could inhibit ECs proliferation, migration, tube formation and inhibit angiogenesis in ex vivo model. Oxygen induced retinopathy and tumor angiogenesis model further show that PEG-GNRs can inhibit angiogenesis in vivo. Gene expression profiles reveal that PEG-GNRs mainly affect ECs cell division process, and PEG-GNRs treated ECs are arrested in G2/M phase. The mechanism is that PEG-GNRs could disrupt TGFβ pathway, and subsequently suppress the assembly of actin filaments in contractile ring site. These findings indicate that PEG-GNR is a novel cytokinesis inhibitor which can be used to interfere with retinal angiogenesis and tumor.

病理性血管生成由内皮细胞（ECs）不受控制的生长所驱动，这可能导致视网膜病变，肿瘤和类风湿性关节炎等。ECs必须经历多个细胞分裂过程才能生长，胞质分裂是最后一步。本研究表明，聚乙二醇化的GNRs（PEG-GNRs）特异地靶向EC的胞质分裂过程，这导致了高比例的双核细胞，而这些双核EC失去了增殖能力。进一步的数据表明，PEG-GNRs在体外和体内均不引起毒性。在离体模型中，PEG-GNRs可以抑制ECs的增殖，迁移，管形成并抑制血管生成。氧诱导的视网膜病变和肿瘤血管生成模型进一步表明PEG-GNRs可以抑制血管生成体内。基因表达谱显示，PEG-GNRs主要影响ECs的细胞分裂过程，而经PEG-GNRs处理的ECs被阻滞在G2 / M期。其机制是PEG-GNRs可能破坏TGFβ途径，并随后抑制肌动蛋白丝在收缩环位点的组装。这些发现表明PEG-GNR是一种新型的胞质分裂抑制剂，可用于干扰视网膜血管生成和肿瘤。