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一种新型双模态成像剂,针对乳腺癌的 HER2 分子。

A Novel Bimodal Imaging Agent Targeting HER2 Molecule of Breast Cancer.

机构信息

Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.

State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

出版信息

J Immunol Res. 2018 Mar 6;2018:6202876. doi: 10.1155/2018/6202876. eCollection 2018.

Abstract

Nanobubble (NB), a newly developed nanoscaled ultrasound contrast agent (UCA) for molecular imaging, has been widely researched for these years. Targeting it with functional molecule, nanobubble can adhere selectively to cellular epitopes and receptors outside the vasculature via enhanced permeability and retention (EPR) effect of tumor blood vessel. To enhance the targeting rate of our previous prepared NBs-Affibody for HER2 (+) breast cancer imaging, we introduced a near-infrared fluorescent (NIRF) dye, IR783, in this study to enhance tumor-specific targeting rate and provide a promising modality for dual-mode imaging. The prepared IR783-NBs-Affibody presented a uniform nanoscale size around 482.7 ± 54.3 nm, good biosecurity, and stability over time. The encapsulation efficiency (EE) of IR-783 was 15.09% in the conjugates leading to a successful NIR fluorescence and ultrasound enhancement imaging ex vivo. IR783-NBs-Affibody was able to automatically accumulate on BT474 cells with a highly increased targeting rate of 85.4% compared with previous NBs-Affibody of 26.6%, while Affibody-guided HER2 binding was only found in HER2-positive cell lines (BT474 and T-47D). The newly developed IR783-NBs-Affibody is characterized with favorable HER2 targeting ability and bimodal imaging capability for breast cancer. Thus, IR783-NBs-Affibody holds great potential in molecular diagnosis for patients with breast cancer.

摘要

纳米气泡(NB)是一种新开发的纳米级超声对比剂(UCA),近年来在分子成像方面得到了广泛研究。通过肿瘤血管的增强通透性和滞留(EPR)效应,用功能分子对纳米气泡进行靶向处理,纳米气泡可以选择性地黏附在血管外的细胞表位和受体上。为了提高我们之前制备的用于 HER2(+)乳腺癌成像的 NB-Affibody 的靶向率,我们在这项研究中引入了一种近红外荧光(NIRF)染料 IR783,以提高肿瘤特异性靶向率,并为双模成像提供一种有前途的方式。所制备的 IR783-NB-Affibody 呈现出约 482.7±54.3nm 的均匀纳米级尺寸、良好的生物安全性和随时间的稳定性。IR-783 的包封效率(EE)在缀合物中为 15.09%,导致成功的近红外荧光和超声增强成像在体外。与之前的 26.6%的 NB-Affibody 相比,IR783-NB-Affibody 能够自动积聚在 BT474 细胞上,靶向率高达 85.4%,而 Affibody 介导的 HER2 结合仅在 HER2 阳性细胞系(BT474 和 T-47D)中发现。新开发的 IR783-NB-Affibody 具有良好的 HER2 靶向能力和用于乳腺癌的双模式成像能力。因此,IR783-NB-Affibody 在乳腺癌患者的分子诊断中具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/118c/5944285/1289464471b9/JIR2018-6202876.001.jpg

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