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适配体偶联载药声敏液滴用于超声治疗。

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

机构信息

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.

出版信息

Biomaterials. 2012 Feb;33(6):1939-47. doi: 10.1016/j.biomaterials.2011.11.036. Epub 2011 Dec 3.

Abstract

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability.

摘要

肿瘤治疗需要多功能的治疗策略,通过特异性靶向治疗来减少一般毒性并提高疗效。在这项研究中,我们制备并功能测试了适体偶联和阿霉素(DOX)负载的声滴,其包含液态全氟戊烷化合物和基于脂质的壳材料的核心。sgc8c 适体的偶联提供了特异性靶向 CCRF-CEM 细胞进行成像和治疗的能力。高强度聚焦超声(HIFU)被引入以触发靶向声滴蒸发(ADV),这导致通过惯性空化的机械性癌细胞破坏和通过局部药物释放的化学治疗。HIFU 照射显示具有适体偶联的液滴的细胞活力降低了 56.8%,与非偶联的液滴相比增加了 4.5 倍。此外,与非蒸发或部分蒸发的液滴相比,完全蒸发的液滴导致癌细胞摄取 DOX 的量最高。光学研究清楚地说明了 ADV 靶向 CEM 细胞时发生的瞬态变化,并且 B 型超声成像显示 ADV 导致超声图像中的对比度增强。总之,我们制备的液滴作为一种混合的化学和机械策略,通过超声介导的 ADV 特异性破坏癌细胞,同时提供超声成像能力。

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