用于核酸递送的 GSH 响应型纳米粒构建.

Nucleic acid therapy has received more and more attention in recent years, but nucleic acid drugs are easily cleared quickly, easily degraded by nucleases, non-specific biodistribution and not easily taken up by cells, making it difficult to exert effects in the body. This article provides glutathione (GSH) responsive release nanoparticles capable of effective nucleic acid drug delivery. Methods Use hexadecyltrimethylammonium chloride (CTAC) to prepare mesoporous silicon nanoparticles, modify and activate sulfhydryl groups on the surface of mesoporous silicon nanoparticles, and make them react with sulfhydryl modified polypropylene imine and polyethylene glycol to form mesoporous silicon nanoparticles with GSH response. The particles are loaded with nucleic acid by electrostatic adsorption. The Malvern particle size analyzer measures the surface potential and particle size, and observes the morphology of the nanoparticles with a transmission electron microscope. Nucleic acid electrophoresis is used to detect the nucleic acid loading efficiency, the GSH response to the release of PEI is detected in vitro, and the cell uptake and lysosome escape are observed by confocal microscope. The nanoparticles with GSH response were successfully constructed, with a particle size of 76.44±1.68 nm and a surface potential of 33.93± 0.59 mV. The nanoparticles were observed to be round and porous particles through transmission electron microscopy. The agarose nucleic acid loading experiment demonstrated when the ratio of nitrogen to phosphorus is greater than 20, nucleic acid can be loaded efficiently. Confocal microscopy showed that the nanoparticles could be successfully taken up by MDA-MB-231 breast cancer cells. In the lysosomal escape experiment, it was observed that the fluorescence of Cy5-siRNA separated from the fluorescence of the lysosome after 3 h entering the cell, which proved the established nanoparticles successful escaped from the lysosome. The mesoporous silicon nanoparticles with GSH response have been successfully constructed, which can be effectively used for nucleic acid delivery. [ABSTRACT FROM AUTHOR]