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Cavitation-Enhanced Delivery of the Nanomaterial Graphene Oxide-Doxorubicin to Hepatic Tumors in Nude Mice Using 20 kHz Low-Frequency Ultrasound and Microbubbles
Journal of Nanomaterials Pub Date : 2020-06-29 , DOI: 10.1155/2020/3136078
Zhi Yong Shen 1 , Bei Qi Shen 2 , Ai Jun Shen 1 , Xin Hua Zhu 3
Affiliation  

Graphene oxide (GO) is a kind of nanomaterial. Here, we explored its application in tumor treatment. We loaded doxorubicin onto the surface of GO to form graphene oxide-doxorubicin (GO-DOX). After injection of the contrast agent SonoVue microbubbles (MBs) into the tail vein of tumor-bearing nude mice, subcutaneous hepatic carcinomas inoculated with the HepG2 cell line were irradiated with 20 kHz low-frequency ultrasound (US). Subsequently, GO-DOX was injected into the tail vein of nude mice. Transmission electron microscopy (TEM) and TUNEL assays were performed to observe the curative effects. Biocompatibility tests of GO-DOX included routine blood cell counts, blood smears, serum biochemical assays, and histological sampling of important organs. It was found that the nanomaterial GO-DOX promoted apoptosis of tumor cells in nude mice. TEM of the USMB+GO-DOX treatment showed vascular endothelial cell wall rupture, widened endothelial cell gaps, black granules in the vascular lumen, interstitial erythrocyte leakage, and apparent apoptosis of tumor cells. There were no toxic side effects of GO-DOX on the blood system and in the major organs of these mice. Ultrasound cavitation destroys tumor blood vessels and enhances the release of nanomaterials to tumor cells of nude mice.

中文翻译:

使用20 kHz低频超声和微泡将纳米材料氧化石墨烯-阿霉素空化增强递送至裸鼠的肝肿瘤

氧化石墨烯(GO)是一种纳米材料。在这里,我们探讨了其在肿瘤治疗中的应用。我们将阿霉素加载到GO的表面上,形成氧化石墨烯-阿霉素(GO-DOX)。将造影剂SonoVue微泡(MBs)注入荷瘤裸鼠的尾静脉后,用20 kHz低频超声(US)照射接种了HepG2细胞系的皮下肝癌。随后,将GO-DOX注入裸鼠的尾静脉。进行透射电子显微镜(TEM)和TUNEL测定以观察疗效。GO-DOX的生物相容性测试包括常规血细胞计数,血液涂片检查,血清生化测定以及重要器官的组织学采样。发现纳米材料GO-DOX促进了裸鼠中肿瘤细胞的凋亡。USMB + GO-DOX处理的TEM显示血管内皮细胞壁破裂,内皮细胞间隙变宽,血管腔内出现黑色颗粒,间质红细胞渗漏以及肿瘤细胞的明显凋亡。GO-DOX对这些小鼠的血液系统和主要器官没有毒副作用。超声空化破坏了肿瘤血管并增强了纳米材料向裸鼠肿瘤细胞的释放。
更新日期:2020-06-29
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