Kooiman Klazina, Roovers Silke, Langeveld Simone A G, Kleven Robert T, Dewitte Heleen, O'Reilly Meaghan A, Escoffre Jean-Michel, Bouakaz Ayache, Verweij Martin D, Hynynen Kullervo, Lentacker Ine, Stride Eleanor, Holland Christy K
Department of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Ghent Research Group on Nanomedicines, Lab for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Ultrasound Med Biol. 2020 Jun;46(6):1296-1325. doi: 10.1016/j.ultrasmedbio.2020.01.002. Epub 2020 Mar 10.
Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood-brain and blood-spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.
利用空化核的机械活性产生有益组织生物效应的治疗性超声策略正在积极研发中。循环微泡是研究最广泛的空化核,其机械振荡还可在血流中包裹或屏蔽治疗剂,触发并促进局部摄取。振荡微泡可在附近组织或周围液体中产生应力,以增强药物在脑、脊髓、血管系统、免疫系统、生物膜或肿瘤中的渗透及疗效。本综述总结了近期关于超声与空化核和细胞相互作用、肿瘤治疗、免疫治疗、血脑屏障和血脊髓屏障、超声溶栓、心血管药物递送及超声杀菌的研究。特别提供了显著超声特征、药物递送载体、治疗转运途径以及临床前和临床研究的概述。超声与空化核介导的药物递送的成功实施有可能改变药物全身给药的方式,从而带来更有效的治疗方法和侵入性更小的治疗手段。