用AS1411修饰的外泌体-脂质体混合纳米粒子靶向谷氨酰胺合成酶,抑制脉络膜新生血管。

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Miaomiao Zhang, Xinyue Lu, Lifu Luo, Jinqiu Dou, Jingbo Zhang, Ge Li, Li Zhao, Fengying Sun
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引用次数: 0

摘要

脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(wAMD)视力受损的主要原因。最近的研究验证了减少谷氨酰胺合成酶(GS)抑制新生血管形成的潜力,为治疗各种新生血管相关疾病提供了前景。在这项研究中,我们设计了一种CRISPR/Cas9递送系统,采用核酸适配体AS1411作为靶向分子,外泌体-脂质体杂交纳米颗粒(CAELN)作为载体。利用AS1411与内皮细胞表面核素蛋白的结合亲和力,设计出了能特异性靶向谷氨酰胺合成酶基因(GLUL)的递送系统,从而降低GS水平并持续抑制CNV。CAELN 呈球形,分散均匀。体外细胞研究表明,CAELN 的基因编辑效率为 42.05% 至 55.02%,并具有抑制 HUVEC 细胞新生血管的能力。此外,在 CNV 兔子体内进行的药效学研究表明,CAELN 在恢复核内和核外组织厚度方面具有功效。研究结果表明,GS是抑制病理性CNV的一个新靶点,而AS1411修饰的外泌体-脂质体混合纳米颗粒的开发则代表了一种治疗新生血管相关疾病的新型给药方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization.

Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases.

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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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