State Key Laboratory of Pharmaceutical Biotechnology, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Laboratory of Molecular Engineering and Nanomedicine, Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, SAR, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Adv Sci (Weinh). 2023 Nov;10(31):e2301985. doi: 10.1002/advs.202301985. Epub 2023 Sep 14.
Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.
脉络膜新生血管（CNV）是导致湿性年龄相关性黄斑变性（wAMD）不可逆转视力丧失的关键病理事件。目前，抗血管内皮生长因子（VEGF）药物的抗血管生成疗法已成为治疗 wAMD 的标准方法，但仍存在一些局限性，包括每月玻璃体内注射的安全性问题和对新生血管阻塞的疗效不足。光动力疗法（PDT）与抗血管生成药物联合治疗已成为一种新的治疗模式。本文报道了一种通过静脉注射光激活纳米系统（Di-DAS-VER NPs）实现 wAMD 抗血管生成和光动力联合治疗的新方法。该纳米系统由活性氧（ROS）敏感的达沙替尼（DAS）前药和光敏剂维替泊芬（VER）自组装而成。对患病眼睛进行红光照射后，观察到抗血管生成 DAS 的眼内释放，同时通过 VER 产生的 ROS 选择性地封闭新生血管。值得注意的是，Di-DAS-VER NPs 表现出对 CNV 的良好治疗效果，同时最小化了全身毒性。该研究通过将光激活过程与联合治疗整合到一个简单的纳米系统中，实现了对 wAMD 的高效静脉治疗。
