Department of Internal Medicine III, University of Heidelberg, Germany.
Curr Pharm Des. 2012;18(15):2166-83. doi: 10.2174/138161212800099946.
Ultrasound targeted microbubble destruction (UTMD) has evolved as a novel system for non-invasive, organ- and tissue-specific drug and gene delivery. Initially developed as ultrasound contrast agents, microbubbles (MBs) have increasingly gained attention for their ability to directly deliver different classes of bioactive substances (e.g. genes, drugs, proteins, gene silencing constructs) to various organ systems and tumors. Bioactive substances can be attached to or incorporated in the microbubble shells. Applying ultrasound at their resonance frequency, microbubbles oscillate. When using higher ultrasound energies, oscillation amplitudes increase, finally resulting in microbubble destruction. This leads to increased capillary and cell membrane permeability in the immediate vicinity of the ruptured MBs, thus facilitating tissue and cell penetration of co-administered or loaded bioactive substances. Numerous proof of principle studies have been performed, demonstrating the broad potential of UTMD as a site-specific, non-invasive therapeutic tool, delivering microbubble payload to various target tissues and organ systems or facilitating uptake of bioactive substances into tissues or cells. This review focuses on current in vivo studies and therapeutic approaches of UTMD. Promising results give hope for future clinical applications of this novel non-viral vector system. Nevertheless, several limitations remain, which will also be discussed in this review article.
超声靶向微泡破坏（UTMD）已发展成为一种用于非侵入性、器官和组织特异性药物和基因传递的新系统。微泡（MBs）最初作为超声造影剂开发，因其能够将不同类别的生物活性物质（例如基因、药物、蛋白质、基因沉默构建体）直接递送至各种器官系统和肿瘤而受到越来越多的关注。生物活性物质可以附着或包含在微泡壳中。应用与其共振频率相同的超声，微泡会发生振荡。当使用更高的超声能量时，振荡幅度会增加，最终导致微泡破裂。这会导致破裂的 MB 附近的毛细血管和细胞膜通透性增加，从而促进共给药或加载的生物活性物质进入组织和细胞。已经进行了大量的原理验证研究，证明了 UTMD 作为一种具有广泛应用潜力的靶向、非侵入性治疗工具的潜力，可将微泡有效载荷递送至各种靶组织和器官系统，或促进生物活性物质进入组织或细胞。本文重点介绍了 UTMD 的当前体内研究和治疗方法。有前途的结果为这一新的非病毒载体系统的未来临床应用带来了希望。然而，仍然存在一些限制，本文也将对此进行讨论。
