Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy.

尽管过去已经对纳米药物进行了广泛的癌症治疗研究，但是纳米药物在肿瘤部位的不良聚集仍然是一个严重的问题。因此，需要新的药物递送系统来增强纳米药物在肿瘤部位的积累和渗透。近来，高强度聚焦超声（HIFU）已被强调为一种非侵入性的治疗方式，并与纳米药物相结合显示出增强的治疗效果。HIFU和微泡的组合所引起的空化作用会导致细胞膜的通透性暂时增强，从而促进药物向肿瘤部位的递送效率的提高。因此，我们结合微泡介绍了HIFU的声空化和热/机械效应，以克服常规药物输送的局限性。HIFU强大的声能将空化效应最大化，从而诱导了从纳米药物-微泡复合物局部释放的纳米药物在肿瘤中的优先积累。此外，HIFU的机械作用使积聚的纳米药物渗透到更深的肿瘤区域。与低频超声（美国）相比，HIFU优先积累纳米药物并使其更深入地渗透显示出增强的治疗效果。这些总体结果表明，将纳米药物-微泡复合物与HIFU结合使用的策略是用于癌症治疗的有前途的工具。HIFU的机械作用使积累的纳米药物渗透到更深的肿瘤区域。与低频超声（美国）相比，HIFU优先积累纳米药物并使其更深入地渗透显示出增强的治疗效果。这些总体结果表明，将纳米药物-微泡复合物与HIFU结合使用的策略是用于癌症治疗的有前途的工具。HIFU的机械作用使积累的纳米药物渗透到更深的肿瘤区域。与低频超声（美国）相比，HIFU优先积累纳米药物并使其更深入地渗透显示出增强的治疗效果。这些总体结果表明，将纳米药物-微泡复合物与HIFU结合使用的策略是用于癌症治疗的有前途的工具。