脑靶向硫化银量子点的构建及体外跨血脑屏障作用

doi:10.3969/j.issn.2095-9400.2020.03.008

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Abstract Objective: To design the brain targeted Ag2S and Ag2S-PEG quantum dots and evaluate the property of the modified quantum dots in crossing the in vitro blood-brain barrier. Methods: Ag2S was conjugated with Angiopep-2 (Ag2S-ANG) and Ag2S-PEG was conjugated with Angiopep-2 (Ag2S-PEG-ANG) through the condensation reaction of amino and carboxyl groups mediated by EDC and NHS. The structure and size of Ag2S, Ag2S-ANG, Ag2S-PEG, Ag2S-PEG-ANG were characterized by agarose electrophoresis, dynamic light scattering transmission, electron microscope (TEM). The property of four kinds of quantum dots across the blood-brain barrier was evaluated in vitro by using the in vitro blood-brain barrier model. The cytotoxicity of four kinds of materials on U87 MG and bEnd.3 cells was observed. Results: Ag2S-ANG and Ag2S-PEG-ANG had a shorter migration distance compared with Ag2S and Ag2S-PEG in the agarose gel electrophoresis. The hydrate particle size of Ag2S-ANG and Ag2S-PEG-ANG was respectively increased compared with Ag2S and Ag2S-PEG. And their Zeta potential exhibited electropositive reinforcement. From the TEM results, we founded that the partical size of Ag2S-ANG and Ag2S-PEG-ANG was bigger than Ag2S and Ag2S-PEG (P<0.05). Ag2S, Ag2S-ANG, Ag2S-PEG, Ag2S-PEG-ANG QDs had no obvious cytotoxicity when the concentration was lower than 100 μg/mL. In vitro blood-brain barrier cell model, Ag2S-ANG, Ag2S-PEG and Ag2S-PEG-ANG quantum dots could cross the bEnd.3 cells in the upper layer, especially when the uptake of Ag2S-ANG was 6 times that of Ag2S by U87 MG cells in the lower layer (P<0.01). Conclusion: Brain targeted Ag2S-ANG and Ag2S-PEG-ANG are synthesized successfully. Ag2S-ANG QDs exhibit excellent ability to cross the blood-brain barrier system in vitro and target glioma cells, which lays the foundations for further study of in vivo brain targeting imaging.

Key words： Ag2S quantum dot brain-targeting angiopep-2 blood brain barrier

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	XU Yi
	YAN Meiling
	MA Jifei
	ZHAO Fangfei
	SUN Yanhong
	WANG Lihua
	GAO Jimin

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https://xb.wmu.edu.cn/EN/10.3969/j.issn.2095-9400.2020.03.008 OR https://xb.wmu.edu.cn/EN/Y2020/V50/I3/206

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