The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, People's Republic of China.
Department of Ophthalmology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People's Republic of China.
Int J Nanomedicine. 2024 Nov 21;19:12369-12387. doi: 10.2147/IJN.S492363. eCollection 2024.
Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.
Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.
The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of -28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.
This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.
氧化应激、异常血管生成和炎症是导致眼部新生血管疾病（ONDs）发展的三个关键因素。本研究旨在开发一种多功能纳米药物 DEX@MPDA-Arg@Si（DMAS），它集成了介孔聚多巴胺、血管内皮生长因子（VEGF）-siRNA 和地塞米松（DEX），以解决这些治疗靶点。
通过透射电子显微镜和纳米颗粒粒径分析仪测量 DMAS 的理化性质。通过紫外可见分光光度计测量 DMAS 的包封效率和载药量。使用三种已建立的小鼠模型评估 DMAS 的体内治疗效果和眼部安全性，包括碱烧伤诱导的角膜新生血管化（CoNV）模型、氧诱导的视网膜病变（OIR）模型和激光诱导的脉络膜新生血管化（CNV）模型。
DMAS 纳米颗粒呈均匀的碗状，平均粒径为 264.9±2.5nm，zeta 电位为-28.2±4.2mV。它们表现出高载药效率（DEX 为 36.04±3.60%）和良好的生物相容性。体外研究证实了其具有强大的抗氧化、抗炎和抗凋亡特性。在体内，DMAS 治疗在所有模型中均具有显著的治疗效果。它有效地抑制了 CoNV，促进了角膜修复，并调节了碱烧伤模型中的炎症。在 OIR 模型中，DMAS 通过降低 VEGF 表达来减少视网膜新生血管化。在激光诱导的 CNV 模型中，它显著减少了 CNV 面积和病变厚度。
本研究开发了一种多功能纳米药物 DMAS，能够共递 VEGF-siRNA 和 DEX，为治疗 ONDs 提供协同治疗益处。DMAS 纳米药物具有潜在的抗炎、抗氧化和抗血管生成作用，突出了其作为多种眼部疾病的多功能有效治疗方法的潜力。
