pH调控Y型分子筛负载阿霉素纳米药物制备及与MM⁃231细胞的作用  

pH Regulated Nanomedicine Based on Y⁃Type Molecular Sieve Loading Doxorubicin:Preparation and Interaction with MM⁃231 Cells

作　　者：任晶[1] 闫锦慧 张安懿 闫宇星 王存存 李林 REN Jing;YAN Jin-Hui;ZHANG An-Yi;YAN Yu-Xing;WANG Cun-Cun;LI Lin(Department of Chemistry,Taiyuan Normal University,Jinzhong,Shanxi 030619,China;Humic Acid Engineering and Technology Research Center of Shanxi Province,Jinzhong,Shanxi 030619,China)

机构地区：[1]太原师范学院化学系,晋中030619 [2]山西省腐植酸工程技术研究中心,晋中030619

出　　处：《无机化学学报》2022年第1期93-102,共10页Chinese Journal of Inorganic Chemistry

基　　金：山西省自然科学基金青年基金(No.201801D221440);山西省高等学校科技成果转化培育项目(No.2020CG048);山西省高等学校科技创新计划项目(No.2021L434);太原师范学院大学生创新创业训练项目(No.CXCY2129,CXCY2130)资助。

摘　　要：针对抗肿瘤小分子药物靶向性差、疗效低和毒副性大等缺陷,我们以Y型分子筛(YMS)为基体、阿霉素(DOX)为药物模型,通过pH调控,借助氢键和范德华力等物理作用力制备得到高负载Y型分子筛纳米药物体系(YMS⁃DOX)。采用UV⁃Vis、FT⁃IR、粒径和电位测试及荧光光谱证实YMS⁃DOX成功制备,且DOX的负载率可高达99.61%。体外药物释放测试发现YMS⁃DOX具有pH响应释放特性,在肿瘤环境中(pH=4.5)的药物释放量为正常生理环境(pH=7.4)中的3.8倍,表明其具有良好的药物输送特性。此外,利用流式细胞术和MTT测试法探究了YMS⁃DOX对乳腺癌细胞(MM⁃231)和树突细胞(DC)的细胞凋亡和毒性,结果表明YMS⁃DOX可以诱导肿瘤细胞凋亡,且可降低对正常细胞的毒副作用。To overcome the shortcomings of poor antitumor drug targeting,low efficacy,and high toxicity,a pH regu⁃lated drug delivery system(YMS⁃DOX)through hydrogen bonds and van der Waals force was constructed to acquire high drug loading capacity and better therapeutic efficiency based on Y⁃type molecular sieve(YMS)as nano⁃carrier and doxorubicin(DOX)as the model drug.The successful formation of YMS⁃DOX was confirmed by using UV⁃Vis,FT⁃IR,particle size and potential measurement,and fluorescence spectroscopy.Interestingly,with the assistance of citric acid buffer solution(pH=9.0),YMS nanocarrier loading DOX achieved nearly 99.61%loading efficiency.In vitro drug release showed that YMS had low premature drug release under physiological conditions(pH=7.4),while greatly enhanced in the tumor microenvironment(pH=4.5)3.8 times compared to normal tissue,indicating YMS⁃DOX can be effectively released in the tumor site.Excitingly,when dendritic(DC)cells and breast cancer(MM⁃231)cells were treated with YMS⁃DOX,the results demonstrated that YMS⁃DOX preferentially accumulated much more in tumor cells than in normal cells,which implies that YMS⁃DOX can selectively kill tumor cells.In addition,assessment by flow cytometry apoptosis assay illustrated that YMS⁃DOX could induce cell apoptosis and inhibit cell migration.

关 键 词：Y型分子筛 阿霉素 pH调控 高负载 乳腺癌治疗 

分 类 号：O647.33[理学—物理化学] TB34[理学—化学]