Liu Min-Chao, Liu Bing, Chen Xian-Li, Lin Hui-Chao, Sun Xiang-Yu, Lu Jia-Zheng, Li Yan-Yu, Yan Si-Qi, Zhang Lu-Yong, Zhao Ping
1 School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou, China.
2 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
J Biomater Appl. 2018 Mar;32(8):1090-1104. doi: 10.1177/0885328217752994. Epub 2018 Jan 22.
Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO. The formation of the MMSN-FA-CaCO was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO to HeLa cells. The present data suggest that the CaCO coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.
制备了磁性介孔二氧化硅纳米球(MMSN),并用癌细胞特异性配体叶酸对其表面进行修饰。然后使用碳酸钙作为酸活化的门控剂来封闭MMSN的介孔,即MMSN-FA-CaCO。通过几种表征技术,即透射电子显微镜、ζ电位测量、傅里叶变换红外光谱、BET表面积测量和紫外可见光谱,证明了MMSN-FA-CaCO的形成。柔红霉素成功负载在MMSN-FA-CaCO中,该系统在血液或肿瘤微环境下表现出敏感的pH刺激响应释放特性。叶酸受体(FR)过表达的HeLa细胞对MMSN-FA-CaCO的细胞摄取高于未偶联叶酸的细胞。细胞内摄取研究表明,这些纳米颗粒优先摄取到FR阳性[FR(+)]HeLa细胞中,而不是FR阴性[FR(-)]A549细胞系中。DAPI染色实验表明,MMSN-FA-DNM-CaCO对HeLa细胞具有较高的凋亡率。目前的数据表明,MMSN的CaCO包衣和叶酸修饰能够为癌症治疗中的药物递送系统创建一个靶向、pH敏感的模板。