高效黏膜穿透的近红外光驱动的黏惰性纳米马达  

Near-infrared Light-driven Mucus-inert Janus Nanomotors for Efficient Mucus Penetration

作　　者：刘玲 姬发 余林玲 孙彦[1,2] LIU Ling;JI Fa;YU Linling;SUN Yan(Department of Biochemical Engineering,School of Chemical Engineering and Technology;Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology,Ministry of Education,Tianjin University,Tianjin 300350,China)

机构地区：[1]天津大学化工学院生物化工系 [2]教育部合成生物工程重点实验室,天津300350

出　　处：《高等学校化学学报》2023年第6期60-70,共11页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21878223,21621004);天津市自然科学基金(批准号:19JCQNJC05200)资助。

摘　　要：黏液层覆盖在黏膜上方,是人体的免疫防线,其在利用静电和疏水作用高效吸附并滞留外来粒子的同时也阻碍了载药纳米粒子的穿透,这给基于纳米载体的跨黏膜疾病的治疗带来困难.本文制备了一种近红外光驱动的具有黏液惰性的纳米马达,用于快速穿透黏液层进行黏膜递送.该纳米马达以表面氨基化的介孔二氧化硅纳米粒子作为主体,将两性离子聚合物聚羧基甜菜碱甲基丙烯酸酯(pCBMA)接枝于其上得到黏液惰性的纳米粒子MSNs-pCBMA;随后,通过将金沉积在MSNs-pCBMA半表面上得到Janus型纳米马达JMSNs-pCBMA,其可以在近红外光的照射下定向运动.透射电子显微镜、傅里叶变换红外光谱、X射线能谱和热重分析等表征结果表明合成了JMSNs-pCBMA,水合粒径为(329±14)nm,pCBMA的接枝量为0.114 g/g.光热响应实验表明,JMSNs-pCBMA溶液在近红外光照射下具有良好的升温能力.此外,黏液渗透实验表明,pCBMA的接枝和近红外光驱动均提高了纳米粒子在黏液中的渗透能力,其中JMSNs-pCBMA在近红外光照射4 h后黏液渗透率达到了52.4%,表观渗透系数达到21.9×10^(-6)cm/s,且在黏液中的运动速度为3.28μm/s.体外细胞实验表明,JMSNs-pCBMA具有良好的生物相容性,可在体外被Calu-3细胞高效摄取.本文制备了一种具有快速穿透黏液层能力的纳米马达,为跨黏液层递送载体的构建提供了新思路,将推动纳米马达在黏膜递送中的应用.The mucus layer is a crucial immune barrier located on the mucosal epithelial surface,which adheres foreign particles through the electrostatic and hydrophobic interactions,and thus hinders the mucus penetration of drug-loaded nanoparticles.Herein,a near-infrared-driven mucus-inert Janus nanomotor(JMSNs-pCBMA)was synthesized for the transmucosal delivery,based on the mesoporous silica nanoparticles,super hydrophilic zwitterionic poly carboxybetaine methacrylate(pCBMA)grafting,and gold depositing on the half surface.The transmission electron microscopy(TEM),Fourier transform infrared spectrophotometer(FTIR),energy dispersive X-ray spectrometry(EDX)and thermogravimetric analysis showed that JMSNs-pCBMA was synthesized with hydrodynamic size of(329±14)nm and pCBMA grafting density of 0.114 g/g.JMSNs-pCBMA exhibited the excellent ability to increase temperature rapidly under near-infrared light irradiation.The mucus-containing Transwell experiments showed that both of the pCBMA grafting and near-infrared light irradiation improved the permeability of nanomotor in mucus,and penetration percentage of JMSNs-pCBMA in mucus reached 52.4%in 4 h with an apparent permeability coefficient of 21.9×10^(-6)cm/s.In addition,the speed of JMSNs-pCBMA in mucus under near-infrared light irradiation reached 3.28μm/s.In vitro cell experiments showed that JMSNs-pCBMA had good biocompatibility and could be endocytosed effectively by Calu-3 cells.In conclusion,a novel near-infrared light-driven nanomotor with fast mucus penetration and effective mucosal epithelial cell uptake was obtained for transmucosal delivery,and the experimental results would benefit the design and application of nanocarriers in the diagnosis,treatment and imaging of mucosal-related diseases.

关 键 词：纳米马达 两性离子聚合物 黏液屏障 近红外光驱动 

分 类 号：O622[理学—有机化学] TQ460[理学—化学]