Targeted long-term noninvasive treatment of choroidal neovascularization by biodegradable nanoparticles

• Published in: Acta biomaterialia 2023-08, Vol.166, p.536-551
• Main Authors: Yao, Hao, Xu, Huan, Wu, Mingxing, Lei, Wulong, Li, Lanjiao, Liu, Danning, Wang, Zhigang, Ran, Haitao, Ma, Huafeng, Zhou, Xiyuan
• Format: Article
• Language: English
• Subjects: Angiopoietin1; Animals; CD105; Choroidal neovascularization; Choroidal Neovascularization - metabolism; Disease Models, Animal; Drug delivery; Endothelial Cells - metabolism; Inflammation; Nanoparticles - therapeutic use; Rats; Wet Macular Degeneration - drug therapy
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2023.05.021

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. 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. [Display omitted]