光靶向纳米颗粒静脉治疗脉络膜新生血管。
Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles.
机构信息
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
出版信息
Nat Commun. 2019 Feb 18;10(1):804. doi: 10.1038/s41467-019-08690-4.
Choroidal neovascularization (CNV) is the major cause of vision loss in wet age-related macular degeneration (AMD). Current therapies require repeated intravitreal injections, which are painful and can cause infection, bleeding, and retinal detachment. Here we develop nanoparticles (NP-[CPP]) that can be administered intravenously and allow local drug delivery to the diseased choroid via light-triggered targeting. NP-[CPP] is formed by PEG-PLA chains modified with a cell penetrating peptide (CPP). Attachment of a DEACM photocleavable group to the CPP inhibits cellular uptake of NP-[CPP]. Irradiation with blue light cleaves DEACM from the CPP, allowing the CPP to migrate from the NP core to the surface, rendering it active. In mice with laser-induced CNV, intravenous injection of NP-[CPP] coupled to irradiation of the eye allows NP accumulation in the neovascular lesions. When loaded with doxorubicin, irradiated NP-[CPP] significantly reduces neovascular lesion size. We propose a strategy for non-invasive treatment of CNV and enhanced drug accumulation specifically in diseased areas of the eye.
脉络膜新生血管（CNV）是湿性年龄相关性黄斑变性（AMD）导致视力丧失的主要原因。目前的治疗方法需要反复进行玻璃体内注射，这既痛苦又可能导致感染、出血和视网膜脱离。在这里，我们开发了可以通过静脉内给药的纳米颗粒（NP-[CPP]），并通过光触发靶向使药物能够局部递送至患病的脉络膜。NP-[CPP]由聚乙二醇-聚乳酸链修饰的细胞穿透肽（CPP）形成。将 DEACM 光可裂解基团连接到 CPP 上会抑制 NP-[CPP]的细胞摄取。用蓝光照射从 CPP 上裂解 DEACM，使 CPP 从 NP 核心迁移到表面，从而使其具有活性。在激光诱导的 CNV 小鼠中，静脉注射与眼部辐照偶联的 NP-[CPP]允许 NP 在新生血管病变中积累。当负载多柔比星时，辐照的 NP-[CPP]可显著减小新生血管病变的大小。我们提出了一种非侵入性治疗 CNV 的策略，并增强了药物在眼部病变区域的积累。
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