Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound.
Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound.
复制标题
低强度聚焦超声触发相变纳米液滴的药物释放
作者：
Cao Y;Chen Y;Yu T;Guo Y;Liu F;Yao Y;Li P;Wang D;Wang Z;Chen Y;Ran H
背景：超声作为最有效的触发剂之一，具有组织穿透能力强、无创等特点，在控制药物释放、提高化疗疗效方面显示出巨大的潜力。在这项研究中，我们首次报道了一种可编程低强度聚焦超声(LIFU)相变给药纳米系统的构建，该系统可以触发药物释放并显著提高抗癌药物的给药能力。方法：将气-液相变全氟碳(全氟戊烷)和抗癌药物阿霉素(阿霉素)同时包裹在两种纳米微粒中。通过触发LIFU，纳米液滴可以在肿瘤组织中局部转化为微泡进行声学成像，微泡破裂后，加载的抗癌药物(阿霉素)就会释放出来。根据壳层材料的声学性质，如壳层硬度等，在不同的声压水平下激活了两种类型的纳米液滴(脂基纳米液滴和PLGA基纳米液滴)。测试并选择利福的超声辐照时间和功率来监测和控制纳米微滴中药物的释放。采用不同的超声能量(3W/3min和8W/3min)在体外诱导纳米液滴的相变和微泡崩塌。结果：我们在药物释放曲线中检测到三个步骤，显示出可编程的模式。重要的是，随着利福的暴露，药物在肿瘤内的积累和分布显著增加，肿瘤的增殖受到实质性的抑制。两个载药纳米微滴的联合传递可以克服化疗过程中肿瘤组织的物理障碍。结论：本研究为可编程LIFU纳米载体超声触发化疗提供了一种新的策略，可实现药物的按需释放。
Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release.