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超声聚焦靶向基因传递的生物合成纳米气泡。

Biosynthetic nanobubbles for targeted gene delivery by focused ultrasound.

机构信息

Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China.

出版信息

Nanoscale. 2019 Aug 8;11(31):14757-14768. doi: 10.1039/c9nr03402a.

DOI:10.1039/c9nr03402a
PMID:31348476
Abstract

Ultrasound-targeted microbubble destruction (UTMD) has recently drawn considerable attention in biomedicine applications due to its great potential to locally enhance gene delivery. However, conventional microbubbles have a microscale particle size and polydisperse particle size distribution, which makes it difficult for them to directly come into contact with tumor cells and to efficiently deliver therapeutic genes via ultrasound cavitation effects. In the current study, we developed a kind of novel cationic biosynthetic nanobubble (CBNB) as an ultrasonic gene delivery carrier through coating PEI on the surface of these biosynthetic nanobubbles (BNBs). The BNBs, produced from an extremely halophilic archaeon (Halobacterium NRC-1), possess a nanoscale size and can produce stable contrast signals both in vitro and in vivo. Surface modification with PEI polymer greatly increased the DNA loading capability of BNBs, leading to significantly improved gene transfection efficiency when combining with ultrasound. To our knowledge, this is the first report to apply biosynthetic bubbles as non-viral gene carriers which can effectively deliver genes into tumor cells with the aid of ultrasound cavitation. Our study provides a powerful tool for image-guided and efficient gene delivery using biosynthetic nanoscale contrast agents.

摘要

超声靶向微泡破坏(UTMD)最近在生物医学应用中引起了相当大的关注,因为它具有局部增强基因传递的巨大潜力。然而,传统的微泡具有微观颗粒尺寸和多分散的颗粒尺寸分布,这使得它们难以直接与肿瘤细胞接触,并通过超声空化效应有效地传递治疗基因。在本研究中,我们通过在这些生物合成纳米泡(BNB)的表面涂覆 PEI,开发了一种新型阳离子生物合成纳米泡(CBNB)作为超声基因传递载体。BNB 由一种极端嗜盐古菌(Halobacterium NRC-1)产生,具有纳米级尺寸,在体外和体内均可产生稳定的对比信号。PEI 聚合物的表面修饰大大提高了 BNB 的 DNA 负载能力,当与超声结合时,显著提高了基因转染效率。据我们所知,这是首次应用生物合成气泡作为非病毒基因载体的报告,可在超声空化的帮助下将基因有效递送至肿瘤细胞。我们的研究为使用生物合成纳米级对比剂进行图像引导和高效基因传递提供了一种强大的工具。

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