Intravenous anti-VEGF agents with RGD peptide-targeted core cross-linked star (CCS) polymers modified with indocyanine green for imaging and treatment of laser-induced choroidal neovascularization
Intravenous anti-VEGF agents with RGD peptide-targeted core cross-linked star (CCS) polymers modified with indocyanine green for imaging and treatment of laser-induced choroidal neovascularization
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DOI：
10.1039/c9bm02086a
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发表时间：
2020-08-21
影响因子：
6.6
通讯作者：
Yu, Jing
中科院分区：
文献类型：
--
作者：
Cai, Wenting;Chen, Qijing;Yu, Jing
视网膜相关性黄斑变性（AMD）是老年人中不可逆视力丧失的主要原因，其中湿性AMD的特征在于脉络膜新生血管（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（CNV）。合成了S-PEG-ICG-RGD-RBZ纳米粒，并通过ZP、DLS、UV-Vis、TEM和考马斯亮蓝染色分析进行表征。在我们的研究中，S-PEG-ICG-RGD-RBZ纳米粒在体外和体内均表现出良好的生物相容性。体外实验表明，在所研究的浓度范围内，纳米粒无细胞毒性、死亡细胞、凋亡和遗传毒性;静脉注射纳米粒对心、肝、脾、肺、肾和脑等体内器官无组织学损伤和凋亡。所设计的纳米颗粒在体外抑制VEGF诱导的细胞增殖、迁移、小管形成以及CD 31和VEGF的表达。同时，在体内研究也表明，抑制CNV的发展的NPs。此外，静脉注射经吲哚菁绿色修饰的NPs后，CNV区域成像。NP主要针对CNV区域，并且不保留在其他器官中。总之，用RGD修饰的S-PEG被设计为将抗VEGF剂递送至CNV区域的强大载体。具有良好细胞相容性的智能纳米粒子在CNV治疗中具有巨大的药物递送潜力。
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 biocompatibilityin vitroandin vivo. There was no cellular toxicity, dead cells, apoptosis or genotoxicity in the studied concentration rangein vitro; meanwhile, intravenous injection of the designed NPs did not cause histological damage or apoptosis in the organsin 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 VEGFin vitro. Meanwhile,in vivostudies 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.