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
作者单位E-mail
任晶 太原师范学院化学系, 晋中 030619 jing2008_1231@126.com 
闫锦慧 太原师范学院化学系, 晋中 030619  
张安懿 太原师范学院化学系, 晋中 030619  
闫宇星 太原师范学院化学系, 晋中 030619  
王存存 太原师范学院化学系, 晋中 030619  
李林 太原师范学院化学系, 晋中 030619
山西省腐植酸工程技术研究中心, 晋中 030619 
lilin@tynu.edu.cn 
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。
关键词: Y型分子筛  阿霉素  pH调控  高负载  乳腺癌治疗
基金项目: 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)和太原师范学院大学生创新创业训练项目(No.CXCY2129,CXCY2130)资助。
Abstract: To overcome the shortcomings of poor antitumor drug targeting, low efficacy, and high toxicity, a pH regulated 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 YMSDOX 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.
Keywords: Y-type molecular sieve  doxorubicin  pH regulating  high loading  breast cancer therapy
投稿时间:2021-07-14 修订日期:2021-10-19
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任晶,闫锦慧,张安懿,闫宇星,王存存,李林.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[J].无机化学学报,2022,38(1):93-102.
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