Abstract：
Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. STATEMENT OF SIGNIFICANCE: This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration.
摘要：
脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(AMD)患者视力下降的主要原因。目前,这些疾病的治疗需要反复的玻璃体内注射，这可能导致感染和出血等并发症。所以,我们已经开发了一种用纳米颗粒治疗CNV的非侵入性方法，即,血管生成素1-抗CD105-PLGA纳米颗粒（AAPNP），其靶向CNV以增强药物在位点的积累。这些纳米粒子，以PLGA为载体，可以缓慢释放包封的血管生成素1(Ang1)和靶向脉络膜新生血管标志物CD105来增强药物积累，增加血管内皮细胞之间的血管内皮钙粘蛋白（VE-cadherin）表达，有效减少新生血管渗漏，抑制血管生成素2（Ang2）的分泌。在激光诱导CNV的大鼠模型中,静脉注射AAPNP在减少CNV渗漏和面积方面具有良好的治疗效果。总之,这些合成AAPNP为AMD提供了一种有效的替代治疗方法,满足了新生血管性眼病无创治疗的迫切需要.重要性声明：这项工作描述了合成，注射介导的递送，具有包封的Ang1的靶向纳米颗粒的体外和体内功效；通过这些纳米颗粒，该药物可针对脉络膜新生血管病变进行持续治疗。Ang1的释放可有效减少新生血管渗漏,维持血管稳定，并抑制Ang2分泌和炎症。抗CD105不仅可以将颗粒靶向到该部位，还可以增加新血管形成抑制的疗效。本研究为湿性年龄相关性黄斑变性的治疗提供了新的途径。
