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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.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-06-20 , DOI: 10.1039/c9bm02086a Wenting Cai 1 , Qijing Chen , Tianyi Shen , Qian Yang , Weinan Hu , Peng Zhao , Jing Yu
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-06-20 , DOI: 10.1039/c9bm02086a Wenting Cai 1 , Qijing Chen , Tianyi Shen , Qian Yang , Weinan Hu , Peng Zhao , Jing Yu
Affiliation
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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.
中文翻译：
静脉注射抗VEGF药物，配以吲哚菁绿修饰的RGD肽靶向的核心交联星（CCS）聚合物，用于成像和治疗激光诱导的脉络膜新生血管。
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的特征是脉络膜新血管形成（CNV）。我们在本文中开发了具有良好生物安全性的纳米颗粒，可有效治疗脉络膜新血管形成（CNV）。合成了S-PEG-ICG-RGD-RBZ NP，并通过ZP，DLS，UV-Vis，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 NPs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，凋亡或遗传毒性；同时，静脉注射设计的NPs不会引起器官的组织学损伤或细胞凋亡在体内，包括心脏，肝脏，脾脏，肺脏，肾脏和大脑。设计的NP在体外抑制VEGF诱导的增殖，细胞迁移，管形成以及CD31和VEGF的表达。同时，体内研究也表明NP抑制CNV的发展。此外，静脉注射经吲哚菁绿修饰的NP后，CNV区域成像。NPs主要针对CNV区域，没有保留在其他器官中。总之，经RGD修饰的S-PEG被设计为将抗VEGF剂递送至CNV区域的有力载体。具有良好细胞相容性的智能NP在CNV治疗中具有巨大的药物输送潜力。
更新日期：2020-08-11
中文翻译：
静脉注射抗VEGF药物，配以吲哚菁绿修饰的RGD肽靶向的核心交联星（CCS）聚合物，用于成像和治疗激光诱导的脉络膜新生血管。
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的特征是脉络膜新血管形成（CNV）。我们在本文中开发了具有良好生物安全性的纳米颗粒，可有效治疗脉络膜新血管形成（CNV）。合成了S-PEG-ICG-RGD-RBZ NP，并通过ZP，DLS，UV-Vis，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 NPs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，凋亡或遗传毒性；同时，静脉注射设计的NPs不会引起器官的组织学损伤或细胞凋亡在体内，包括心脏，肝脏，脾脏，肺脏，肾脏和大脑。设计的NP在体外抑制VEGF诱导的增殖，细胞迁移，管形成以及CD31和VEGF的表达。同时，体内研究也表明NP抑制CNV的发展。此外，静脉注射经吲哚菁绿修饰的NP后，CNV区域成像。NPs主要针对CNV区域，没有保留在其他器官中。总之，经RGD修饰的S-PEG被设计为将抗VEGF剂递送至CNV区域的有力载体。具有良好细胞相容性的智能NP在CNV治疗中具有巨大的药物输送潜力。
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