Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan.
J Control Release. 2010 Sep 15;146(3):291-8. doi: 10.1016/j.jconrel.2010.05.033. Epub 2010 Jun 2.
Ultrasound-mediated microbubble destruction may enhance the release of nanoparticles from vasculature to tumor tissues. In this study, we used four different sizes of lipid-coated CdSe quantum dot (LQD) nanoparticles ranging from 30 to 180 nm, 1.0-MHz pulsed focused ultrasound (FUS) with a peak acoustic pressure of 1.2-MPa, and an ultrasound contrast agent (UCA; SonoVue) at a dose of 30 microL/kg to investigate any enhancement of targeted delivery. Tumor-bearing male Balb/c mice were first injected with UCA intravenously, were then sonicated at the tumors with FUS, and were finally injected with 50 microL of the LQD solution after the sonication. The mice were sacrificed about 24h after the sonication, and then we quantitatively and qualitatively evaluated the deposition of LQDs in the tumors by using graphite furnace atomic absorption spectrometry (GF-AAS), photoluminescence spectrometry (PL), and harmonic generation microscopy (HGM). Further, immunoblotting analysis served to identify the biochemical markers reflecting the vascular rupture. The experimental results show that the amount of LQDs deposited in tumor tissues was greater in cases of FUS/UCA application, especially for smaller LQDs, being 4.47, 2.27, 0.99, and 0.82 (microg Cd)/(g tumor) for 30, 80, 130, and 180 nm of LQDs, respectively; compared to 1.12, 0.75, 0.26, and 0.34 (microg Cd)/(g tumor) in absence of FUS/UCA. The immunoblotting analysis further indicates that FUS-induced UCA oscillation/destruction results in rupture areas in blood vessels increasing the vascular permeability and thus justifying for the higher quantity of nanoparticles deposited in tumors.
超声介导的微泡破坏可能会增强纳米粒子从血管向肿瘤组织的释放。在这项研究中,我们使用了四种不同大小的脂质包覆的 CdSe 量子点(LQD)纳米粒子,范围从 30 到 180nm,1.0MHz 脉冲聚焦超声(FUS),峰值声压为 1.2MPa,以及超声造影剂(SonoVue)的剂量为 30μL/kg,以研究任何靶向递送的增强作用。荷瘤雄性 Balb/c 小鼠首先静脉注射 UCA,然后用 FUS 在肿瘤处进行超声处理,最后在超声处理后注射 50μL 的 LQD 溶液。在超声处理后约 24 小时处死小鼠,然后通过石墨炉原子吸收光谱(GF-AAS)、光致发光光谱(PL)和二次谐波产生显微镜(HGM)定量和定性地评估 LQD 在肿瘤中的沉积。此外,免疫印迹分析用于鉴定反映血管破裂的生化标志物。实验结果表明,在 FUS/UCA 应用的情况下,LQD 在肿瘤组织中的沉积量更大,尤其是对于较小的 LQD,分别为 30、80、130 和 180nm 的 LQD 的 4.47、2.27、0.99 和 0.82(μg Cd)/(g 肿瘤);与不存在 FUS/UCA 的情况下的 1.12、0.75、0.26 和 0.34(μg Cd)/(g 肿瘤)相比。免疫印迹分析进一步表明,FUS 诱导的 UCA 振荡/破坏导致血管破裂区域增加,血管通透性增加,从而证明了更多数量的纳米粒子沉积在肿瘤中。