O'Neill Brian E, Vo Howard, Angstadt Mary, Li King P C, Quinn Tim, Frenkel Victor
Diagnostic Radiology Department, Clinical Center, National Institute of Health, Bethesda, MD 20892, USA.
Ultrasound Med Biol. 2009 Mar;35(3):416-24. doi: 10.1016/j.ultrasmedbio.2008.09.021. Epub 2008 Dec 10.
High intensity focused ultrasound (HIFU) is generally thought to interact with biological tissues in two ways: hyperthermia (heat) and acoustic cavitation. Pulsed mode HIFU has recently been demonstrated to increase the efficacy of a variety of drug therapies. Generally, it is presumed that the treatment acts to temporarily increase the permeability of the tissue to the therapeutic agent, however, the precise mechanism remains in dispute. In this article, we present evidence precluding hyperthermia as a principal mechanism for enhancing delivery, using a quantitative analysis of systemically administered fluorescent nanoparticles delivered to muscle in the calves of mice. Comparisons were carried out on the degree of enhancement between an equivalent heat treatment, delivered without ultrasound, and that of the pulsed-HIFU itself. In the murine calf muscle, Pulsed-HIFU treatment resulted in a significant increase in distribution of 200 nm particles (p < 0.016, n = 6), while the equivalent thermal dose showed no significant increase. Additional studies using this tissue/agent model also demonstrated that the pulsed HIFU enhancing effects persist for more than 24 h, which is longer than that of hyperthermia and acoustic cavitation, and offers the possibility of a novel third mechanism for mediating delivery.
高强度聚焦超声（HIFU）通常被认为以两种方式与生物组织相互作用：热疗（加热）和声空化。最近已证明脉冲模式HIFU可提高多种药物治疗的疗效。一般认为，该治疗作用是暂时增加组织对治疗剂的通透性，然而，确切机制仍存在争议。在本文中，我们通过对全身给药至小鼠小腿肌肉中的荧光纳米颗粒进行定量分析，提供了排除热疗作为增强递送主要机制的证据。对在无超声情况下进行的等效热处理与脉冲HIFU本身之间的增强程度进行了比较。在小鼠小腿肌肉中，脉冲HIFU治疗导致200nm颗粒的分布显著增加（p < 0.016，n = 6），而等效热剂量则未显示出显著增加。使用该组织/试剂模型的其他研究还表明，脉冲HIFU的增强作用持续超过24小时，这比热疗和声空化的作用时间更长，并提供了介导递送的新型第三种机制的可能性。
