Angiopep-2-conjugated Ag2S Quantum Dot for NIR-II Imaging of Brain Tumors

doi:10.6023/A18010039

Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (5): 393-399.DOI: 10.6023/A18010039 Previous Articles Next Articles

Article

Angiopep-2修饰的Ag₂S量子点用于近红外二区脑胶质瘤成像

徐毅^a,b, 赵彦^b, 张叶俊^c, 崔之芬^b, 王丽华^b, 樊春海^b, 高基民^a, 孙艳红^b

a 温州医科大学检验医学院、生命科学学院温州 325000;
b 中国科学院上海应用物理研究所微观界面物理与探测重点实验室物理生物学研究室上海 201800;
c 苏州影睿光学科技有限公司苏州 215123

投稿日期:2018-01-26 发布日期:2018-03-16
通讯作者: 高基民,E-mail:jimingao64@163.com;孙艳红,E-mail:sunyanhong@sinap.ac.cn E-mail:jimingao64@163.com;sunyanhong@sinap.ac.cn
基金资助:
项目受国家自然科学基金（Nos.11575278，21675167，11675251，61475181，61378062）、国家重点研发计划（Nos.2016YFA0201200，2016YFA0400902）和中国科学院前沿科学重点研究（No.QYZDJ-SSW-SLH031-02）资助.

Angiopep-2-conjugated Ag₂S Quantum Dot for NIR-II Imaging of Brain Tumors

Xu Yi^a,b, Zhao Yan^b, Zhang Yejun^c, Cui Zhifen^b, Wang Lihua^b, Fan Chunhai^b, Gao Jimin^a, Sun Yanhong^b

a School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325000;
b CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800;
c Suzhou Near-Infrared Optics Technology Co., Ltd., Suzhou 215123

Received:2018-01-26 Published:2018-03-16
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 11575278, 21675167, 11675251, 61475181, 61378062), the Ministry of Science and Technology of China (Nos. 2016YFA0201200, 2016YFA0400902) and the Key Research Program of Frontier Sciences (No. QYZDJ-SSW-SLH031-02).

1. Angiopep-2-conjugated Ag₂S Quantum Dot for NIR-II Imaging of Brain Tumors.PDF(139KB)

Abstract

Ag₂S quantum dot with excellent NIR-Ⅱ fluorescence can provide deeper tissue penetration (>1.1 cm) and higher spatiotemporal resolution (25 μm, 50 ms) in comparison to the conventional fluorophore. In this study, we designed a NIR-Ⅱ probe based Ag₂S quantum dot for imaging of brain tumor. Angiopep-2 was used to modify Ag₂S quantum dot, which is a 19-mer peptide exhibiting high binding efficiency with low-density lipoprotein receptor-related protein-1 (LRP-1) of blood brain barrier and glioma. Due to the surface of Ag₂S quantum dots with carboxyl groups and angiopep-2 peptide with amino groups, Ag₂S was conjugated with Angiopep-2 (Ag₂S-ANG) through the condensation reaction of amino and carboxyl groups mediated by EDC and NHS. The structure, size and spectral properties of Ag₂S-ANG were characterized by agarose electrophoresis, dynamic light scattering transmission, electron microscope (TEM), UV-vis spectrometer and NIR fluorescence spectrometer, respectively. Results showed that Ag₂S-ANG had a short migration distance compared with Ag₂S in the agarose gel electrophoresis. The hydrate particle size of Ag₂S was approximately 6 nm, Ag₂S-ANG was approximately 8 nm and its zeta potential exhibited electropositive reinforcement, zeta potential of Ag₂S is -11.47±1.56 mV and Ag₂S-ANG is +28.7±1.35 mV. Ag₂S-ANG exhibited similar absorbance and fluorescence spectra to Ag₂S, except a slight enhancement of emission peak. These results indicated that Ag₂S-ANG was synthesized successfully. We further observed its cell cytotoxicity, distribution and uptake in Uppsala 87 Malignant Glioma cells(U87MG), and in vivo distribution in the solid tumor-bearing mouse. Ag₂S-ANG had no obvious cytotoxicity when the concentration is inferior to 100 μg/mL and had more uptake in U87MG cells than that of Ag₂S. In animal experiments, glioma tumor-bearing mice were used to investigate the distribution and tumor targeting of Ag₂S-ANG. Results showed that Ag₂S-ANG can distribute and accumulate in subcutaneous tumor site, indicating that Ag₂S-ANG had the potential of targeting the glioma cells.

Key words: Ag₂S quantum dot, brain-targeting, angiopep-2, NIR-II imaging References

Cite this article

Xu Yi, Zhao Yan, Zhang Yejun, Cui Zhifen, Wang Lihua, Fan Chunhai, Gao Jimin, Sun Yanhong. Angiopep-2-conjugated Ag₂S Quantum Dot for NIR-II Imaging of Brain Tumors[J]. Acta Chim. Sinica, 2018, 76(5): 393-399.

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Angiopep-2修饰的Ag₂S量子点用于近红外二区脑胶质瘤成像

Angiopep-2-conjugated Ag₂S Quantum Dot for NIR-II Imaging of Brain Tumors

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Angiopep-2修饰的Ag2S量子点用于近红外二区脑胶质瘤成像