聚乙二醇修饰的金纳米棒抑制视网膜新生血管形成的作用与机制研究

Retinal neovascularization (RNV) is the common pathological changes of ocular fundus diseases which could lead to blindness ultimately, and there is no effective therapy up to now. Nanoscale material usually possess unique structure and physicochemical property, which showed unlimited potential in the field of biological medicine. In our previous study, we synthesized high-purity PEGYlated Gold Nanorods (PEGYlated GNRs), and found that they could selectively inhibit human retinal endothelial cell (HREC) proliferation while had no inhibition effect on normal cells. Meanwhile, our preliminary experimental results indicated that PEGYlated GNRs could inhibit HREC cell cycle at cytokenesis phase while had no effect on cell apoptosis, suggesting that PEGYlated GNRs was a well targeted nanoscale material to vascular without severe cytotoxicity. On this foundation, we will use transmission electron microscope(TEM), flow cytometry, confocal microscopy and inductive coupled plasma mass spectrometry (ICP-MS) to investigate the toxicity of PEGYlated GNRs, and to investigate the effect and mechanism of PEGYlated GNRs on RNV in vitro and in vivo, which will provide novel clues for RNV treatment.

视网膜新生血管(Retinal neovascularization,RNV)是一类严重致盲性疾病的病理改变，目前尚无很好的治疗方法。纳米材料因其粒径极小，具有特殊结构和理化性质，在生物医药领域展现出无限潜力。我们在前期研究中合成了高纯度的聚乙二醇修饰的金纳米棒(PEGYlated GNRs)，并发现其可以特异性的抑制视网膜血管内皮细胞 (HREC) 增殖，而对多种正常细胞无影响。同时，预实验结果显示PEGYlated GNRs可以抑制HREC细胞周期于胞质分裂期而不诱导其凋亡，表明PEGYlated GNRs是一个血管靶向性好、毒性小的纳米材料。在此基础上，本研究将利用透射电镜、流式细胞仪、蛋白免疫印迹、激光扫描共聚焦和电感耦合等离子体质谱等技术方法，在体内和体外新生血管模型上探索PEGYlated GNRs毒性及其抑制RNV形成的作用及机制，从而为RNV的治疗提供新思路。

视网膜新生血管（retinal neovascularization, RNV）是多种视网膜疾病的共同病理改变如早产儿视网膜病变、视网膜静脉周围炎、糖尿病视网膜病变和缺血性视网膜静脉阻塞等，可以造成严重的视力损害。在本项工作中，我们证明金纳米棒可以抑制血管内皮细胞增殖、迁移、管样形成、主动脉环出芽以及改善氧诱导小鼠视网膜病变。进一步研究发现，金纳米棒可以明显影响细胞骨架蛋白-微丝的组装，而不影响微管的功能。不同于多数纳米颗粒通过促进细胞凋亡或坏死发挥作用，金纳米棒可以抑制视网膜血管内皮细胞于胞质分裂期，而不引起细胞凋亡。这种靶向性作用于分裂期细胞的特性 ，可能在增殖性新生血管病变的治疗中发挥重要作用。本研究首次发现金纳米棒对血管内皮细胞有特殊的靶点，同时对新生血管性疾病有高效的抑制作用。相关研究发表JCR一区SCI论文一篇（Song Hongyuan#, Guo Ting#, Zhao Zichang, Wei Youheng, Luo Haoyang, Weng Weizong, Zhang Rui, Zhong Ming, Chen Chunying*, Su Jiacan*, Shen Wei*, Biocompatible PEGylated gold nanorods function as cytokinesis inhibitors to suppress angiogenesis. Biomaterials 2018, 178:23-35 IF 10.317），获得国家发明型专利一项。