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。

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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引用次数: 0

摘要

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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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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来源期刊
Nano Letters
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.
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