Cai Wenting, Chen Qijing, Shen Tianyi, Yang Qian, Hu Weinan, Zhao Peng, Yu Jing
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, China.
Biomater Sci. 2020 Aug 21;8(16):4481-4491. doi: 10.1039/c9bm02086a. Epub 2020 Jul 1.
Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss among elderly persons, of which wet AMD is characterized by choroidal neovascularization (CNV). We herein developed nanoparticles with good biosafety for effective treatment of choroidal neovascularization (CNV). S-PEG-ICG-RGD-RBZ NPs were synthesized and characterized by ZP, DLS, UV-Vis, TEM and Coomassie Brilliant Blue staining analyses. In our study, the S-PEG-ICG-RGD-RBZ NPs exhibited good biocompatibility in vitro and in vivo. There was no cellular toxicity, dead cells, apoptosis or genotoxicity in the studied concentration range in vitro; meanwhile, intravenous injection of the designed NPs did not cause histological damage or apoptosis in the organs in vivo, including the heart, liver, spleen, lung, kidneys and brain. The designed NPs inhibited VEGF-induced proliferation, cell migration, tube formation and expression of CD31 and VEGF in vitro. Meanwhile, in vivo studies also indicated the inhibition of CNV development by NPs. What's more, the CNV area was imaged after intravenous injection of NPs modified with indocyanine green. The NPs were mainly targeted to CNV areas and did not remain in the other organs. In summary, S-PEG modified with RGD was designed as a powerful carrier to deliver anti-VEGF agents to CNV areas. The smart NPs, which have good cellular compatibility, hold great potential for drug delivery in CNV treatment.
年龄相关性黄斑变性（AMD）是老年人不可逆视力丧失的主要原因，其中湿性AMD的特征是脉络膜新生血管形成（CNV）。我们在此开发了具有良好生物安全性的纳米颗粒，用于有效治疗脉络膜新生血管形成（CNV）。合成了S-PEG-ICG-RGD-RBZ纳米颗粒，并通过Zeta电位（ZP）、动态光散射（DLS）、紫外可见光谱（UV-Vis）、透射电子显微镜（TEM）和考马斯亮蓝染色分析对其进行了表征。在我们的研究中，S-PEG-ICG-RGD-RBZ纳米颗粒在体外和体内均表现出良好的生物相容性。在体外研究的浓度范围内没有细胞毒性、死细胞、细胞凋亡或基因毒性；同时，静脉注射设计的纳米颗粒在体内不会对包括心脏、肝脏、脾脏、肺、肾脏和大脑在内的器官造成组织学损伤或细胞凋亡。设计的纳米颗粒在体外抑制了血管内皮生长因子（VEGF）诱导的增殖、细胞迁移、管腔形成以及CD31和VEGF的表达。同时，体内研究也表明纳米颗粒对CNV发展有抑制作用。此外，在用吲哚菁绿修饰的纳米颗粒静脉注射后对CNV区域进行了成像。纳米颗粒主要靶向CNV区域，不会滞留在其他器官中。总之，用RGD修饰的S-PEG被设计为一种强大的载体，可将抗VEGF药物递送至CNV区域。这些具有良好细胞相容性的智能纳米颗粒在CNV治疗的药物递送方面具有巨大潜力。
