介孔二氧化硅作为无机纳米药物载体的构建及生物活性  

Construction of mesoporous silica as an inorganic nano-drug carrier and its bioactivity

作　　者：刘莹 史巍[2] 龚锐[3] 朱宏明 Liu Ying;Shi Wei;Gong Rui;Zhu Hong-ming(Department of Pharmaceutical Preparation Section,SINO-SIGAPORE ECO-CITY Hospital of Tianjin Medical University,Tianjin 300467,China;Department of Hepatopancreatobiliary Surgery,3Department of Pharmacy,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学中新生态城医院药剂科,天津市300467 [2]天津医科大学第二医院肝胆胰外科,天津市300211 [3]天津医科大学第二医院药学部,天津市300211

出　　处：《中国组织工程研究》2018年第26期4144-4149,共6页Chinese Journal of Tissue Engineering Research

基　　金：天津市卫生局科技基金(2014KZ093):自制免疫磁珠分选泌尿系肿瘤干细胞的应用研究;天津市卫生局科技基金(2014KZ109):胰腺癌患者外周血循环肿瘤细胞分选研究~~

摘　　要：背景:目前已有大量基于介孔二氧化硅平台构建刺激响应药物运输体系的报道,但在控制循环过程中仍存在药物泄露情况。目的:研究介孔二氧化硅纳米药物载体(MS@FcA A/P@CD@RGD)的制备方法及生物活性。方法:利用MCM-41型介孔二氧化硅纳米颗粒作为细胞内控制药物释放的载体,在其孔道中包载二茂铁和荧光探针,再用β-环糊精堵孔,用整合素抑制剂RGD作为靶向基团,合成介孔二氧化硅纳米药物载体MS@FcAA/P@CD@RGD。以人宫颈癌细胞HeL a和人乳腺癌细胞MCF-7分别作为目标细胞和对照细胞进行MTT实验,评价不同质量浓度介孔二氧化硅纳米药物载体的细胞毒性。将传代后的HeLa细胞分3组培养,分别加入含佛波酯(诱导细胞生成大量H_2O_2)+MS@FcAA/P@CD@RGD的培养基、含二甲基亚砜(清除细胞内H_2O_2)+MS@FcAA/P@CD@RGD的培养基、含MS@FcAA/P@CD@RGD培养基,培养3 h后,利用激光共聚焦显微镜观察纳米颗粒荧光的变化,评价该纳米载药体系对细胞内H_2O_2的响应情况。结果与结论:(1)当介孔二氧化硅纳米药物载体质量浓度在10-100 mg/L范围内时,均有85%以上的He La细胞和MCF-7细胞存活;(2)与加入含MS@FcAA/P@CD@RGD培养基的HeL a细胞比较,加入佛波酯+MS@FcAA/P@CD@RGD的HeLa细胞荧光强度明显升高,加入二甲基亚砜+MS@FcAA/P@CD@RGD的HeLa细胞荧光强度明显降低;(3)结果表明,介孔二氧化硅纳米药物载体对细胞毒性很小,对内源性过氧化氢有一定的响应。BACKGROUND： Numerous studies have addressed the construction of stimulating response drug transport systems based on the mesoporous silica platform; however, drug leakage is still inevitable in the control cycle. OBJECTIVE： To study the preparation and bioactivity of mesoporous silica （MS@FcAA/P@CD@RGD）. METHODS： MCM-41 mesoporous silica nanoparticles were used as a release carrier of intracellular controlled drugs. In the channel, ferrocene and fluorescent probes were packaged, and reoccupied using beta-cyclodextrin, and integrin inhibitors RGD were used as targeted groups to synthesize mesoporous silica nanoparticles （MS@FcAA/P@CD@RGD）. MTT assay was performed on human cervical cancer cel l line HeLa and human breast cancer cell MCF-7 as target cells and control cells, respectively, to evaluate the cytotoxicity of mesoporous silica nano-drug carriers with different mass concentrations. The passaged HeLa cells were cultured in three groups： a medium containing phorbol ester （induced a large amount of H2O2 in cells）＋MS@FcAA/P@CD@RGD, a medium containing dimethyl sulfoxide （removal of intracellular H2O2）＋MS@FcAA/P@CD@RGD, or a medium containing MS@FcAA/P@CD@RGD. Then the particle size was measured by Laser scanning confocal microscope, and the response of the nano-drug delivery system to intracellular H2O2 was assessed at 3 days after culture. RESULTS AND CONCLUSION： When the mesoporous silica nanoparticles were within the concentration of 10-100 mg/L, over 85 % of the cells were alive. Compared with the cells cultured in the medium containing MS@FcAA/P@CD@RGD, the fluorescence intensity of HeLa cells with phorbol ester were significantly increased, while the fluorescence intensity of HeLa cells with dimethyl sulfoxide were significantly reduced. To conclude, mesoporous silica nanoparticles have a low cytotoxicity, and have certain response to endogenous hydrogen peroxide.

关 键 词：介孔二氧化硅 纳米药物载体 活性氧 毒性 生物材料 

分 类 号：R318[医药卫生—生物医学工程]