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碘标记的抗血管内皮生长因子受体2靶向介孔二氧化硅纳米粒子在间变性甲状腺癌中的抗肿瘤作用

Antitumor Effect of I-Labeled Anti-VEGFR2 Targeted Mesoporous Silica Nanoparticles in Anaplastic Thyroid Cancer.

作者信息

Zhang Ruiguo, Zhang Yueqian, Tan Jian, Wang Hanjie, Zhang Guizhi, Li Ning, Meng Zhaowei, Zhang Fuhai, Chang Jin, Wang Renfei

机构信息

Department of Nuclear Medicine, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China.

School of Life Sciences, Tianjin University, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, 300072, China.

出版信息

Nanoscale Res Lett. 2019 Mar 14;14(1):96. doi: 10.1186/s11671-019-2924-z.

Abstract

Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor because of its resistance to conventional therapy. Vascular endothelial growth factor receptor (VEGFR)-targeted therapeutics-loaded mesoporous silica nanoparticles represent a major advance for angiogenesis imaging and inhibition in lethal cancers. In the present study, we aimed to assess whether I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles would have antitumor efficacy in an ATC tumor-bearing nude mouse model. Using in vitro and in vivo studies, we investigated the increased targeting ability and retention time in the anti-VEGFR2 targeted group using confocal microscopy and a γ counter. The tumor tissue radioactivity of the anti-VEGFR2 targeted group at 24 and 72 h after intratumoral injection was significantly higher than that of the non-targeted groups (all P < 0.05). Moreover, we found that radioactive accumulation was obvious even at 3 week post-injection in the anti-VEGFR2 targeted group via single-photon emission computed tomography/computed tomography, which was not seen at 3 day post-injection in the NaI group. Meanwhile, compared with the non-targeted group, tumor growth in the targeted group was significantly inhibited, without causing apparent systemic toxic effects. Additionally, the median survival time in the targeted group (41 days) was significantly prolonged compared with that in the non-targeted (34 days) or NaI (25 days) groups (both P < 0.01). Our data support the view that the as-developed I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles showed promising results in ATC tumor-bearing mouse model and such an approach might represent a novel therapeutic option for ATC.

摘要

间变性甲状腺癌(ATC)约占所有甲状腺癌的2%,由于其对传统治疗具有抗性,其生存中值率仍然很低。负载血管内皮生长因子受体(VEGFR)靶向治疗药物的介孔二氧化硅纳米颗粒代表了致死性癌症血管生成成像和抑制方面的一项重大进展。在本研究中,我们旨在评估I标记的抗VEGFR2靶向介孔二氧化硅纳米颗粒在ATC荷瘤裸鼠模型中是否具有抗肿瘤疗效。通过体外和体内研究,我们使用共聚焦显微镜和γ计数器研究了抗VEGFR2靶向组中靶向能力的增强和保留时间。瘤内注射后24小时和72小时,抗VEGFR2靶向组的肿瘤组织放射性显著高于非靶向组(所有P < 0.05)。此外,我们发现通过单光子发射计算机断层扫描/计算机断层扫描,抗VEGFR2靶向组在注射后3周时放射性积累仍很明显,而碘化钠组在注射后3天时未观察到这种情况。同时,与非靶向组相比,靶向组的肿瘤生长受到显著抑制,且未引起明显的全身毒性作用。此外,靶向组的生存中值时间(41天)与非靶向组(34天)或碘化钠组(25天)相比显著延长(两者P < 0.01)。我们的数据支持这样一种观点,即所开发的I标记抗VEGFR2靶向介孔二氧化硅纳米颗粒在ATC荷瘤小鼠模型中显示出有前景的结果,并且这种方法可能代表了一种针对ATC的新型治疗选择。

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