袁宁宁,谢鹏波,李善吉
YUAN Ningning,XIE Pengbo,LI Shanji

• 1:广州工程技术职业学院

摘要(Abstract)：

目的构建一种具有氧化还原刺激响应的核壳纳米载体(MSN-SS-CS/DOX),以增强抗肿瘤药物对细胞的抑制效果。方法壳聚糖(chitosan,CS)通过二硫键偶联到介孔硅纳米粒子表面,以阿霉素(adriamycin,DOX)为模型药物,构建负载抗肿瘤药物的具有氧化还原刺激响应的核壳纳米载体,表征其粒径、电位、微观形态和体外、胞内释放行为,并以细胞凋亡率和细胞活性评价其抗肿瘤细胞效果。结果纳米载体平均粒径在110 nm左右,具有明显的核壳结,并且内部介孔硅纳米粒子(mesoporous silica nanoparticles,MSNs)介孔结构有序;在肿瘤细胞内高浓度谷胱甘肽(glutathione,GSH)还原作用下,壳聚糖膜脱离纳米粒子表面,药物快速释放。MSN-SS-CS使胞内DOX累积浓度显著提高,细胞凋亡率上升了总数量的38.6%。结论所设计的纳米载体具有良好的生物安全性和氧化还原刺激响应性,有效控制抗肿瘤药物在肿瘤细胞内的靶向释放,抗肿瘤效果显著增强。
Objective To prepare redox-responsive nanocarriers for anticancer drug based on chitosan functionalized mesoporous silica nanoparticles( M SNs). Methods Chitosan( CS) was equipped with an outer shell as a "gatekeeper " on the nanoparticle surface via a disulfide linker,which fabricates core-shell nanocarriers to control release the anticancer drugs. Doxorubicin( DOX) as a model drug,the characterization of nanocarriers were studied,include particle size,zeta potential,morphology,intracellular and cell the apoptosis rate,cell activity. Results The nanocarriers have an average diameter of 110 nm with uniform pore size. The polymer nanoshell can be clearly observed around the exterior surface of M SN-SS-CS nanoparticles. M eanwhile,the parallel strips can be clearly observed in the core area. The disulfide bonds can be rapidly cleaved by GSH and lead to shed the end-capping chitosan molecules from the surfaces of nanoparticles. The embedded DOX were released from M SN channels. The results of flowcytometry and confocal laser scanning microscopy( CLSM) showed that the M SN-SS-CS/DOX nanoparticles presented high cellular uptake and cytotoxicity to tumor cells. Conclusion The nanocarriers have good biological safety and redox response,and effectively control the targeted release of antitumor drugs in tumor cells. The drug delivery systems showed the significant anticancer effect. The drug delivery systems showed the significant anticancer effect.

关键词(KeyWords)： 介孔硅纳米粒子;壳聚糖;氧化还原刺激响应;控制释放;抗肿瘤
mesoporous silica nanoparticles;chitosan;doxorubicin;redox responsive;anticancer

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 袁宁宁,谢鹏波,李善吉
YUAN Ningning,XIE Pengbo,LI Shanji

DOI: 10.14066/j.cnki.cn21-1349/r.2018.07.002

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