Jiang Pengfei, Choi Andrew, Swindle-Reilly Katelyn E
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 134-140 W Woodruff Ave, Columbus, OH 43210, USA.
Department of Biomedical Engineering, The Ohio State University, 1080 Carmack Rd, Columbus, OH 43210, USA.
Nanoscale. 2020 Aug 28;12(33):17298-17311. doi: 10.1039/d0nr03710a.
Reactive oxidative species (ROS) are the primary mediator of angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF) in the development of wet age-related macular degeneration (AMD). However, the current treatment of AMD currently relies on monthly intravitreal injection of anti-angiogenic therapeutics to inhibit new choroidal angiogenesis. However, repeated injections have been associated with side-effects, are costly, and may lower patient compliance. Moreover, the intraocular oxidative stress-dependent angiogenesis is not alleviated by current treatments, which limits the overall efficacy of the treatment strategy. Recently, nanoparticle-based devices present potential in sustained delivery of angiogenesis inhibitors and excellent capability of scavenging reactive oxygen species (ROS). Nevertheless, limited efforts have been dedicated to the treatment of oxidative stress-related diseases via a combined anti-angiogenesis and anti-oxidization pathway. For this purpose, we developed anti-angiogenetic protein-loaded polydopamine (PDA) nanoparticles for the enhanced treatment of AMD. Remarkably, the PDA nanoparticles could efficiently scavenge ROS to reduce the expression of angiogenic agents. In parallel, the particles were able to controllably release loaded anti-angiogenic drugs in response to oxidative stress.
活性氧（ROS）是湿性年龄相关性黄斑变性（AMD）发展过程中血管生成的主要介质，它通过上调血管内皮生长因子（VEGF）的表达来促进血管生成。然而，目前AMD的治疗依赖于每月一次玻璃体内注射抗血管生成治疗药物以抑制新的脉络膜血管生成。然而，重复注射会带来副作用，成本高昂，并且可能降低患者的依从性。此外，目前的治疗方法并不能缓解眼内氧化应激依赖性血管生成，这限制了治疗策略的整体疗效。最近，基于纳米颗粒的装置在持续递送血管生成抑制剂和清除活性氧（ROS）方面具有潜力。然而，通过联合抗血管生成和抗氧化途径治疗氧化应激相关疾病的研究还比较有限。为此，我们开发了负载抗血管生成蛋白的聚多巴胺（PDA）纳米颗粒，以增强对AMD的治疗效果。值得注意的是，PDA纳米颗粒能够有效清除ROS，从而降低血管生成因子的表达。同时，这些颗粒能够响应氧化应激可控地释放负载的抗血管生成药物。
