磁性介孔二氧化硅纳米粒子担载黄连素及其体外抗肿瘤作用的研究

发布时间：2018-02-21 11:59

本文关键词： 磁-介孔二氧化硅纳米粒子黄连素载药量　出处：《吉林大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景：传统的细胞毒抗肿瘤化疗药物，缺少靶向性，治疗时对正常组织器官亦造成损伤，因而限制了其在临床上的应用。近年来，我国采用中医中药对肿瘤进行治疗已成为肿瘤治疗领域的一大特色。黄连素作为一种异喹啉类的生物碱单体化合物，存在于一系列药用植物中，如黄连、黄柏等，其抗肿瘤效果显著且毒副作用小。然而，黄连素口服吸收差，生物利用度低等缺点限制了其作为抗肿瘤药物的临床应用。随着纳米医学的飞速发展，，纳米材料作为药物载体广泛的应用在肿瘤治疗领域，Janus磁-二氧化硅介孔纳米粒子（M-MSN）由于其具有优良的生物相容性、低毒性、介孔修饰后可控释药、磁靶向性等优点，适合装载小分子化疗药物。本研究初次尝试用Janus磁-介孔二氧化硅纳米载体担载黄连素，并对增加其载药率和体外抗肿瘤活性进行初步探索。内容：采用扩孔剂均三甲苯（TMB）合成大孔径磁-介孔二氧化硅，调整模板剂CTAB在反应体系用量改变纳米粒子形貌，以及通过增加黄连素在反应溶液体系的分散性和溶解度三种方法提高黄连素的载药量，分别对三种载体的形貌进行表征、载药及释药测定，研究空载载体的细胞安全性和Janus磁-介孔纳米药物载体担载黄连素后体外抗肿瘤活性评价。结果： 1.通过TMB构建大孔径的磁-介孔二氧化硅和通过调整模板剂CTAB用量改变纳米粒子的形貌两种方法，磁-介孔二氧化硅纳米粒子形貌发生改变，但不具有均一性，担载黄连素的载药量没有明显提高。采用DMSO作为溶剂改变黄连素的溶解度和分散性的方法合成的Janus磁-介孔二氧化硅形貌均一，担载黄连素的载药率和载药量有明显提高。 2.采用DMSO作为溶剂增加黄连素的溶解度和分散性的方法所合成的Janus磁-介孔二氧化硅黄连素纳米载体系统，黄连素的载药率约为47%，载药量为20%。空载载体细胞安全性良好，50μg/ml浓度以下基本无毒。Janus磁-介孔二氧化硅纳米载体担载黄连素后对肝癌细胞HepG2的细胞毒性随着载药系统的浓度增加而增大，12.5～50μg/ml载体系统（担载黄连素2.5-10μg/ml）与HepG2共孵育48h,其细胞杀伤作用强于等浓度黄连素组。结论：利用TMB扩孔的方法，以及调整CTAB在反应体系中用量两种方法均无法提高黄连素的载药量，而通过增加黄连素在反应体系中溶解度的方法合成的Janus磁-介孔二氧化硅黄连素纳米载体系统，提高了黄连素的载药率和载药量。Janus磁-介孔二氧化硅纳米空载体在50μg/ml浓度以下体外基本无毒。Janus磁-介孔二氧化硅担载黄连素的纳米载药系统对肿瘤细胞杀伤具有剂量依赖性，12.5～50μg/ml载体系统（担载黄连素2.5～10μg/ml）细胞杀伤作用强于等浓度黄连素组。
[Abstract]:Background:. The traditional cytotoxic anti-tumor chemotherapeutic drugs lack of targeting and damage to normal tissues and organs during treatment, which limits their clinical application in recent years. Chinese traditional medicine has become a major feature in the field of tumor treatment. Berberine, as an isoquinoline alkaloid monomer, exists in a series of medicinal plants, such as Coptis chinensis, Cortex Phellodendri, etc. However, the poor absorption of berberine and its low bioavailability limit its clinical application as an antitumor drug. Nanomaterials are widely used as drug carriers in the field of tumor therapy because of their excellent biocompatibility, low toxicity, controlled release after mesoporous modification and magnetic targeting. It is suitable for loading small molecular chemotherapeutic drugs. In this study, Janus magnetic-mesoporous silica nano-carrier was used to support berberine for the first time, and to increase the drug loading rate and anti-tumor activity in vitro. Content:. The large aperture magnetic-mesoporous silica was synthesized by using the pore expander (TMB), and the dosage of template agent CTAB was adjusted to change the morphology of nanoparticles in the reaction system. By increasing the dispersity and solubility of berberine in the reaction solution, the drug loading of berberine was increased, and the morphology of the three carriers was characterized, and the drug loading and drug release were determined. To study the cell safety of no-load carrier and the evaluation of anti-tumor activity of Janus magnetic-mesoporous drug carrier loaded with berberine in vitro. Results:. 1. The morphology of magneto-mesoporous silica with large pore size was changed by TMB and the morphology of nano-particles was changed by adjusting the amount of template CTAB. The amount of berberine loaded was not significantly increased. The morphology of Janus synthesized by using DMSO as solvent to change the solubility and dispersion of berberine was uniform, and the drug loading rate and amount of loaded berberine were improved obviously. 2. The Janus magnetic-mesoporous silica nano-carrier system was synthesized by using DMSO as solvent to increase the solubility and dispersion of berberine. The drug loading rate of berberine is about 47 and the drug load is 20. The safety of the empty carrier cells is good. The cytotoxicity of berberine loaded on the HepG2 cell line of hepatoma cells after carrying berberine on the magnetic mesoporous silica nano-carrier is basically nontoxic under the concentration of 50 渭 g / ml. When the concentration of berberine was increased, and the 50 渭 g / ml carrier system (supported berberine 2.5-10 渭 g / ml) was incubated with HepG2 for 48 h, the cytotoxicity of the cells was stronger than that of the same concentration of berberine group. Conclusion:. The methods of TMB reaming and adjusting the dosage of CTAB in the reaction system could not increase the amount of berberine loaded. The Janus magnetic-mesoporous silica nano-carrier system was synthesized by increasing the solubility of berberine in the reaction system. The drug loading rate and drug load of berberine. Janus magnetic-mesoporous silica nano-space carrier is basically nontoxic in vitro under 50 渭 g / ml. Janus magnetic-mesoporous silica loaded berberine system can kill tumor cells. The cytotoxicity of the 50 渭 g / ml carrier system (supported berberine 2.510 渭 g / ml) was stronger than that of the same concentration of berberine.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1;TQ127.2

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