Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
J Control Release. 2020 Oct 10;326:75-90. doi: 10.1016/j.jconrel.2020.06.008. Epub 2020 Jun 14.
Beyond the emerging field of oncological ultrasound molecular imaging, the recent significant advancements in ultrasound and contrast agent technology have paved the way for therapeutic ultrasound mediated microbubble oscillation and has shown that this approach is capable of increasing the permeability of microvessel walls while also initiating enhanced extravasation and drug delivery into target tissues. In addition, a large number of preclinical studies have demonstrated that ultrasound alone or combined with microbubbles can efficiently increase cell membrane permeability resulting in enhanced tissue distribution and intracellular drug delivery of molecules, nanoparticles, and other therapeutic agents. The mechanism behind the enhanced permeability is the temporary creation of pores in cell membranes through a phenomenon called sonoporation by high-intensity ultrasound and microbubbles or cavitation agents. At low ultrasound intensities (0.3-3 W/cm), sonoporation may be caused by microbubbles oscillating in a stable motion, also known as stable cavitation. In contrast, at higher ultrasound intensities (greater than 3 W/cm), sonoporation usually occurs through inertial cavitation that accompanies explosive growth and collapse of the microbubbles. Sonoporation has been shown to be a highly effective method to improve drug uptake through microbubble potentiated enhancement of microvascular permeability. In this review, the therapeutic strategy of using ultrasound for improved drug delivery are summarized with the special focus on cancer therapy. Additionally, we discuss the progress, challenges, and future of ultrasound-mediated drug delivery towards clinical translation.
除了肿瘤超声分子成像这一新兴领域外，最近超声和造影剂技术的显著进步为治疗性超声介导的微泡振荡铺平了道路，表明这种方法能够增加微血管壁的通透性，同时引发增强的渗出和药物递送到靶组织。此外，大量的临床前研究表明，单独使用超声或结合微泡可以有效地增加细胞膜的通透性，从而导致分子、纳米颗粒和其他治疗剂在组织中的分布和细胞内递药增加。增强通透性的机制是通过高强度超声和微泡或空化剂产生的一种称为声孔的现象在细胞膜上临时产生孔。在低超声强度（0.3-3 W/cm）下，声孔可能是由于微泡以稳定的运动（也称为稳定空化）而振荡引起的。相比之下，在更高的超声强度（大于 3 W/cm）下，声孔通常通过伴随微泡的爆炸式生长和收缩的惯性空化而发生。已经证明，声孔是一种通过微泡增强微血管通透性来提高药物摄取的高效方法。在这篇综述中，总结了使用超声改善药物输送的治疗策略，特别关注癌症治疗。此外，我们还讨论了超声介导的药物输送向临床转化的进展、挑战和未来。
