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利用 RGD 工程化的外泌体提高靶向能力并实现协同血管生成治疗。

The use of RGD-engineered exosomes for enhanced targeting ability and synergistic therapy toward angiogenesis.

机构信息

The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics &Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

出版信息

Nanoscale. 2017 Oct 19;9(40):15598-15605. doi: 10.1039/c7nr04425a.

Abstract

Promoted therapeutic angiogenesis is a major objective in the area of regenerative medicine, and sufficient vascularization of artificial tissues or organs is one of the main difficulties for the realization of tissue engineering methods. The identification of new kinds of pro-angiogenic materials will greatly profit developments in regenerative medicine. The use of exosomes for this intention is a considerably new idea developed in recent years. However, several limitations need to be addressed before their use as clinical therapeutics, including the lack of efficient exosome enrichment and methods to endow exosomes with targeting ability. Herein, we pioneered biomimetic particles with topographic structures for exosome isolation. Using this system, nearly 80% of exosomes were isolated in 30 min. Through a donor cell-assisted membrane modification strategy, the isolated exosomes exhibited increased targeting to blood vessels due to the modified Arg-Gly-Asp (RGD) peptide on the exosome membrane, and simultaneously possessed a synergistic therapeutic angiogenesis effect and angiogenesis imaging attributed to metabolic labeling by click chemistry both in vitro and in vivo. The engineered exosomes represent a potential new therapeutic tool for angiogenesis therapy and imaging in a bio-friendly manner.

摘要

促进治疗性血管生成是再生医学领域的主要目标,而人工组织或器官的充分血管化是实现组织工程方法的主要难点之一。识别新的促血管生成材料将极大地促进再生医学的发展。近年来,外泌体在这方面的应用是一个相当新的想法。然而,在将其用作临床治疗之前,还需要解决几个限制因素,包括缺乏有效的外泌体富集和赋予外泌体靶向能力的方法。在这里,我们率先使用具有拓扑结构的仿生颗粒来分离外泌体。使用该系统,近 80%的外泌体在 30 分钟内被分离出来。通过供体细胞辅助的膜修饰策略,由于外泌体膜上修饰的精氨酸-甘氨酸-天冬氨酸(RGD)肽,分离得到的外泌体表现出增加的血管靶向性,并且由于点击化学的代谢标记,在体外和体内均表现出协同的治疗性血管生成作用和血管生成成像。工程化的外泌体代表了一种具有生物友好性的潜在新的血管生成治疗和成像治疗工具。

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