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超声介导微泡基因传递体系的研究
Research of Ultrasound-Mediated Gene Delivery
超声波能够在不损害人体正常组织的条件下，有效到达人体组织深处。超声造影剂（微泡），能够显著提高血液和组织的背向散射强度，广泛应用于心血管疾病的检测中。超声微泡介导基因转染技术是指通过微泡的空化作用，实现超声波能量在靶向组织处的富集和释放，进而促进此处组织细胞对基因药物的内化，达到高效转染的目的。由于具有无创、高效安全的特点，超声微泡介导在基因治疗中具有很大的优势和潜力。利用微泡的超声成像功能实现对病变组织诊断成像，利用靶向组织处的超声实现时间空间可控的目的基因的释放，利用微泡在超声作用下的“声孔效应”，实现基因对多种生物膜的跨膜传递，达到基因药物的可视化传递与高效可控释放的目的。本文主要从超声造影剂的种类、超声微泡介导基因转染的机理、微泡基因传递体系的构建等方面，详细综述了这一领域最新的研究进展，并对超声微泡介导基因转染的发展进行了展望。
Ultrasound wave can reach the deep tissues without any harm to human body. Ultrasound contrast agent (microbubble), which can highly enhance the ultrasound backscatter intensity, is widely employed in ultrasonography. Through the cavitation effects of microbubbles, the energy of ultrasound wave will be easily accumulated at the targeted tissue and finally released with the collapse of the bubbles, which will further promote the internalization of gene/drug into the cells, leading to the high transfection efficiency. Due to its non-invasiveness and safety, recent ultrasound-mediated gene therapy shows great potential via the combination of the clinic-realizable ultrasound microbubble technology and gene vectors. The ultrasound-mediated gene therapy, can not only be used in disease diagnosis, but also promote the spatio-temporal controlled release of drug/gene by sonicating at the targeted tissue. Furthermore, microbubble-induced sonoporation can be used as the driving force to transfer gene vectors into cells by improving the permeability of different biofilm. These will together provide approach to visualization of gene delivery and efficient controlled gene expression. In this paper, the recent progress is reviewed in details from the following aspects: development of microbubbles, the mechanism and influence factors, and construction of ultrasound-mediated gene delivery system. Challenges and prospects of ultrasound-mediated gene delivery system are also discussed.
Contents
1 Introduction
2 Development of microbubbles
3 Mechanism and influence factors of ultrasound- mediated gene delivery
4 Construction of ultrasound-mediated gene delivery system
4.1 Co-administration system
4.2 Gene-loaded microbubbles
4.3 Gene vector-microbubble conjugation system
5 Challenges and prospects
ultrasound
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