Angiopep-2-conjugated Ag2S Quantum Dot for NIR-II Imaging of Brain Tumors
Acta Chimica Sinica(2018)
Abstract
Ag2S quantum dot with excellent NIR-II fluorescence can provide deeper tissue penetration ( >1.1 cm) and higher spatiotemporal resolution (25 mu m, 50 ms) in comparison to the conventional fluorophore. In this study, we designed a 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 mu g/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.
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Key words
Ag2S quantum dot,brain-targeting,angiopep-2,NIR-II imaging
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