SIOC 中文
ACS
Adv search

Acta Chimica Sinica >

2018 , Vol. 76 >Issue 5: 393 - 399

DOI: https://doi.org/10.6023/A18010039

Article

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

  • Xu Yi ,
  • Zhao Yan ,
  • Zhang Yejun ,
  • Cui Zhifen ,
  • Wang Lihua ,
  • Fan Chunhai ,
  • Gao Jimin ,
  • Sun Yanhong
Expand
  • 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 date: 2018-01-26

  Online 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).

Fold

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 Chimica Sinica, 2018 , 76(5) : 393 -399 . DOI: 10.6023/A18010039

References

[1] Abbott, N. J.; Patabendige, A. A.; Dolman, D. E.; Yusof, S. R.; Begley, D. J. Neurobiol. Dis. 2010, 37, 13.
[2] Tajes, M.; Ramos-Fernandez, E.; Xian, W. J.; Bosch-Morato, M.; Guivernau, B.; Eraso-Pichot, A.; Salvador, B.; Fernandez-Busquets, X.; Roquer, J.; Munoz, F. J. Mol. Membr. Biol. 2014, 31, 152.
[3] Chen, Y.; Liu, L. Adv. Drug Delivery Rev. 2012, 64, 640.
[4] Patabendige, A.; Skinner, R. A.; Abbott, N. J. Brain Res. 2013, 1521, 1.
[5] Pardridge, W. M. Nat. Rev. Drug Discovery 2002, 1, 131.
[6] Jain, S.; Mishra, V.; Singh, P.; Dubey, P. K.; Saraf, D. K.; Vyas, S. P. Int. J. Pharm. 2003, 261, 43.
[7] Cui, Y.; Zhang, M.; Zeng, F.; Jin, H.; Xu, Q.; Huang, Y. ACS Appl. Mater. Interfaces 2016, 8, 32159.
[8] Li, D.; Yang, K.; Li, J. S.; Ke, X. Y.; Duan, Y.; Du, R.; Song, P.; Yu, K. F.; Ren, W.; Huang, D.; Li, X. H.; Hu, X.; Zhang, X.; Zhang, Q. Int. J. Nanomed. 2012, 7, 6105.
[9] Liu, H. L.; Hua, M. Y.; Yang, H. W.; Huang, C. Y.; Chu, P. C.; Wu, J. S.; Tseng, I. C.; Wang, J. J.; Yen, T. C.; Chen, P. Y.; Wei, K. C. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 15205.
[10] Ge, Z.; Pei, H.; Wang, L.; Song, S.; Fan, C. Sci. China, Chem. 2011, 54, 1273.
[11] Pei, H.; Liang, L.; Yao, G. B.; Li, J.; Huang, Q.; Fan, C. H. Angew. Chem., Int. Ed. 2012, 51, 9020.
[12] Yang, F.; Zuo, X.; Li, Z.; Deng, W.; Shi, J.; Zhang, G.; Huang, Q.; Song, S.; Fan, C. Adv. Mater. 2014, 26, 4671.
[13] Yao, G.; Li, J.; Chao, J.; Pei, H.; Liu, H.; Zhao, Y.; Shi, J.; Huang, Q.; Wang, L.; Huang, W.; Fan, C. Angew. Chem., Int. Ed. Engl. 2015, 54, 2966.
[14] Ye, D. K.; Zuo, X. L.; Fan, C. H. Prog. Chem. 2017, 29, 36.
[15] Chen, P.; Pan, D.; Fan, C.; Chen, J.; Huang, K.; Wang, D.; Zhang, H.; Li, Y.; Feng, G.; Liang, P.; He, L.; Shi, Y. Nat. Nanotechnol. 2011, 6, 639.
[16] Yan, H. H.; Wang, L.; Wang, J. Y.; Weng, X. F.; Lei, H.; Wang, X. X.; Jiang, L.; Zhu, J. H.; Lu, W. Y.; Wei, X. B.; Li, C. ACS Nano 2012, 6, 410.
[17] Bruun, J.; Larsen, T. B.; Jolck, R. I.; Eliasen, R.; Holm, R.; Gjetting, T.; Andresen, T. L. Int. J. Nanomed. 2015, 10, 5995.
[18] Kumar, P.; Wu, H.; McBride, J. L.; Jung, K. E.; Kim, M. H.; Davidson, B. L.; Lee, S. K.; Shankar, P.; Manjunath, N. Nature 2007, 448, 39.
[19] Li, J.; Feng, L.; Fan, L.; Zha, Y.; Guo, L.; Zhang, Q.; Chen, J.; Pang, Z.; Wang, Y.; Jiang, X.; Yang, V. C.; Wen, L. Biomaterials 2011, 32, 4943.
[20] Du, Y.; Xu, B.; Fu, T.; Cai, M.; Li, F.; Zhang, Y.; Wang, Q. J. Am. Chem. Soc. 2010, 132, 1470.
[21] Zhang, Y.; Zhang, Y.; Hong, G.; He, W.; Zhou, K.; Yang, K.; Li, F.; Chen, G.; Liu, Z.; Dai, H.; Wang, Q. Biomaterials 2013, 34, 3639.
[22] Zhang, Y.; Hong, G.; Zhang, Y.; Chen, G.; Li, F.; Dai, H.; Wang, Q. ACS Nano 2012, 6, 3695.
[23] Smith, A. M.; Mancini, M. C.; Nie, S. Nat. Nanotechnol. 2009, 4, 710.
[24] Wang, J.; Wu, Y.; Sun, L.; Zeng, F.; Wu, S. Acta Chim. Sinica 2016, 74, 910. (王俊, 武英龙, 孙立和, 曾钫, 吴水珠, 化学学报, 2016, 74, 910.)
[25] Ji, G.; Yan, L.; Wang, H.; Ma, L.; Xu, B.; Tian, W. Acta Chim. Sinica 2016, 74, 917. (纪光, 闫路林, 王慧, 马莲, 徐斌, 田文晶, 化学学报, 2016, 74, 917.)
[26] Wei, Y.; Yang, X.; Ma, Y.; Wang, S.; Yuan, Q. Chin. J. Chem. 2016, 34, 558.
[27] Arshad, A.; Chen, H.; Bai, X.; Xu, S.; Wang, L. Chin. J. Chem. 2016, 34, 576.
[28] Gao, G.; Gong, D.; Zhang, M.; Sun, T. Acta Chim. Sinica 2016, 74, 363. (高冠斌, 龚德君, 张明曦, 孙涛垒, 化学学报, 2016, 74, 363.)
[29] Hong, G.; Robinson, J. T.; Zhang, Y.; Diao, S.; Antaris, A. L.; Wang, Q.; Dai, H. Angew. Chem., Int. Ed. Engl. 2012, 51, 9818.
[30] Li, C.; Li, F.; Zhang, Y.; Zhang, W.; Zhang, X. E.; Wang, Q. ACS Nano 2015, 9, 12255.
[31] Rault, I.; Frei, V.; Herbage, D.; AbdulMalak, N.; Huc, A. J. Mater. Sci.-Mater. Med. 1996, 7, 215.
[32] Demeule, M.; Regina, A.; Che, C.; Poirier, J.; Nguyen, T.; Gabathuler, R.; Castaigne, J. P.; Beliveau, R. J. Pharmacol. Exp. Ther. 2008, 324, 1064.
[33] Demeule, M.; Currie, J. C.; Bertrand, Y.; Che, C.; Nguyen, T.; Regina, A.; Gabathuler, R.; Castaigne, J. P.; Beliveau, R. J. Neurochem. 2008, 106, 1534.
[34] Che, C.; Yang, G.; Thiot, C.; Lacoste, M. C.; Currie, J. C.; Demeule, M.; Regina, A.; Beliveau, R.; Castaigne, J. P. J. Med. Chem. 2010, 53, 2814.
[35] Sun, X.; Pang, Z.; Ye, H.; Qiu, B.; Guo, L.; Li, J.; Ren, J.; Qian, Y.; Zhang, Q.; Chen, J.; Jiang, X. Biomaterials 2012, 33, 916.
[36] Gao, H.; Zhang, S.; Cao, S.; Yang, Z.; Pang, Z.; Jiang, X. Mol. Pharm. 2014, 11, 2755.
[37] Huang, S.; Li, J.; Han, L.; Liu, S.; Ma, H.; Huang, R.; Jiang, C. Biomaterials 2011, 32, 6832.
[38] Zuo, H.; Chen, W.; Cooper, H. M.; Xu, Z. P. ACS Appl. Mater. Interfaces 2017, 9, 20444.
[39] Ren, J.; Shen, S.; Wang, D.; Xi, Z.; Guo, L.; Pang, Z.; Qian, Y.; Sun, X.; Jiang, X. Biomaterials 2012, 33, 3324.
[40] Wei, X.; Zhan, C.; Chen, X.; Hou, J.; Xie, C.; Lu, W. Mol. Pharmaceutics 2014, 11, 3261.
[41] Xin, H.; Jiang, X.; Gu, J.; Sha, X.; Chen, L.; Law, K.; Chen, Y.; Wang, X.; Jiang, Y.; Fang, X. Biomaterials 2011, 32, 4293.
[42] Chen, C.; Duan, Z.; Yuan, Yan.; Li, R.; Pang, L.; Liang, J.; Xu, X.; Wang, J. ACS Appl. Mater. Interfaces 2017, 9, 5864.
[43] Shao, K.; Huang, R.; Li, J.; Han, L.; Ye, L.; Lou, J.; Jiang, C. J. Control. Release 2010, 147, 118.
[44] Shen, J.; Zhan, C.; Xie, C.; Meng, Q.; Gu, B.; Li, C.; Zhang, Y.; Lu, W. J. Drug. Target. 2011, 19, 197.
[45] Tian, T.; Li, J.; Xie, C.; Sun, Y.; Lei, H.; Liu, X.; Xia, J.; Shi, J.; Wang, L.; Lu, W.; Fan, C. ACS Appl. Mater. Interfaces 2018, 10, 3414.

Options
Outlines

/

〈 〉