Reactive Oxygen Species Responsive Supramolecular Prodrug Eyedrops for the Treatment of Choroidal Neovascularization.

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Letters Pub Date : 2024-11-20 Epub Date: 2024-10-28 DOI:10.1021/acs.nanolett.4c02576

Shuting Xu, Jia Li, Kaiqi Long, Weiping Wang

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Abstract

Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.

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用于治疗脉络膜新生血管的活性氧反应超分子原药眼药水。

脉络膜新生血管（CNV）是新生血管性眼底疾病（包括老年性黄斑变性和糖尿病视网膜病变）的标志。传统的眼药水在治疗脉络膜新生血管方面遇到了巨大的挑战，这主要是由于它们在眼内的生物利用度极低，而且可能产生不良的脱靶效应。在此，我们开发了一种眼部渗透性超分子原药眼药水（Di-DAS/P-PCD），用于在 CNV 的氧化微环境中按需递送抗血管生成药物。眼药水纳米制剂由细胞穿透肽修饰的PEG化环糊精（P-PCD）和对活性氧（ROS）敏感的抗血管生成药物达沙替尼原药Di-DAS组成。在激光诱导的 CNV 小鼠模型中，Di-DAS/P-PCD 的每日灌注可显著穿透脉络膜，明显抑制 CNV 的生长，同时表现出良好的生物相容性。我们的研究结果凸显了超分子原药眼药水作为一种靶向治疗 CNV 和其他新生血管性眼病的多功能方法的潜力。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.