巯嘌呤/维拉帕米-介孔氧化硅释药系统的构建及逆转耐药活性研究

doi:10.3969/j.issn.1006-7795.2015.02.002

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (2): 161-165.doi: 10.3969/j.issn.1006-7795.2015.02.002

巯嘌呤/维拉帕米-介孔氧化硅释药系统的构建及逆转耐药活性研究

邢璐¹, 崔纯莹¹, 王玉记², 房晨婕¹, 吴建辉²

1. 首都医科大学化学生物学与药学院药剂学系, 北京 100069;
2. 首都医科大学化学生物学与药学院药物化学系, 北京 100069

收稿日期:2014-12-08 出版日期:2015-04-21 发布日期:2015-04-16
通讯作者: 吴建辉 E-mail:wujianhui01@126.com
基金资助:
"十二五"重大新药创制科技重大专项(2011ZX09302-007-01)。

6-Mercaptopurine/verapamil-mesoporous silica and reversing multidrug resistance

Xing Lu¹, Cui Chunying¹, Wang Yuji², Fang Chenjie¹, Wu Jianhui²

1. Department of Pharmacy, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China;
2. Department of Medicinal Chemistry, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China

Received:2014-12-08 Online:2015-04-21 Published:2015-04-16
Supported by:
This study was supported by Significant New Drugs Creation "Five-year" Plan Special Science and Technology Major(2011ZX09302-007-01).

摘要/Abstract

摘要： 目的制备巯嘌呤/维拉帕米-介孔氧化硅释药系统并评价其逆转耐药作用。方法采用共缩聚法合成介孔氧化硅纳米粒并载药,制备巯嘌呤/维拉帕米-介孔氧化硅释药系统;动态透析法研究该释药系统的体外释药特性;噻唑蓝比色法(MTT法)评价该释药系统的逆转耐药作用及可能机制。结果所制备释药系统的粒径在170~250 nm左右,Zeta电位在-30 mV~-40 mV,微观形态呈球形,均匀分布,具有规则介孔孔道。体外释放显示维拉帕米缓慢释放,6-巯嘌呤加入诱导剂之前无释放,加入诱导剂后释药过程呈现先突释后缓释。MTT法检测显示所制备释药系统与阳性药维拉帕米及同浓度物理混合物相比,具有显著逆转耐药作用。结论所制备的巯嘌呤/维拉帕米-介孔氧化硅释药系统有较好的抗肿瘤活性及逆转耐药作用。

关键词: 介孔氧化硅, 6-巯嘌呤, 多药耐药, 抗肿瘤

Abstract: Objective To prepare 6-mercaptopurine/verapamil-loaded mesoporous silica, to examine its in vitro antitumor activity and to evaluate if it can reverse drug-resistance. Methods The mesoporous silica nanoparticles(MSNS) were synthesized with copolycondensation method. Separately loaded 6-mercaptopurine and verapamil onto MSNS to construct 6-mercaptopurine/verapamil-mesoporous silica. Dynamic dialysis was used to analyze the in vitro drug release. The reversal of drug resistance of 6-mercaptopurine/verapamil-mesoporous silica was evaluated on MCF-7 and MCF-7/ADM cells using MTT assay. Results There are spherical microstructure, uniform distribution and regular mesoporous channels in the prepared carrier system with a grain diameter ranging from 170 nm to 250 nm and the Zeta potential was in the range of -30 mV to -40 mV. The in vitro drug release showed that no 6-mercaptopurine be released before the addition of DTT but 6-mercaptopurine was suddenly and then slowly released with the addition of DTT. The results of MTT assays showed that 6-mercaptopurine/verapamil-mesoporous silica carrier system had a good effect on the reversal of drug-resistance. Conclusion 6-mercaptopurine/verapamil-mesoporous silica carrier system has a good antitumor activity and can reverse drug resistance.

Key words: mesoporous silica nanoparticles, 6-mercaptopurine, multidrug resistance(MDR), antitumor

中图分类号:

邢璐, 崔纯莹, 王玉记, 房晨婕, 吴建辉. 巯嘌呤/维拉帕米-介孔氧化硅释药系统的构建及逆转耐药活性研究[J]. 首都医科大学学报, 2015, 36(2): 161-165.

Xing Lu, Cui Chunying, Wang Yuji, Fang Chenjie, Wu Jianhui. 6-Mercaptopurine/verapamil-mesoporous silica and reversing multidrug resistance[J]. Journal of Capital Medical University, 2015, 36(2): 161-165.

参考文献

[1] Kathawala R J, Gupta P, Ashby C R Jr, et al.The modulation of ABC transporter-mediated multidrug resistance in cancer:A review of the past decade[J]. Drug Resist Updat, 2015,18C:1-17.
[2] Tian W, Liu J, Guo Y, et al. Self-assembled micelles of amphiphilic PEGylated rapamycin for loading paclitaxel and resisting multidrug resistant cancer cells[J]. J Mater Chem B, 2015,3(7):1204-1207.
[3] Marin J J, Monte M J, Blazquez A G, et al. The role of reduced intracellular concentrations of active drugs in the lack of response to anticancer chemotherapy[J]. Acta Pharmacol Sin, 2014,35(1):1-10.
[4] Lu H P, Chao C C. Cancer cells acquire resistance to anticancer drugs:an update[J]. Biomed J, 2012,35(6):464-472.
[5] Wang W, Fang C, Wang X, et al. Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy[J]. Nanoscale, 2013,5(14):6249-6253.
[6] Lin V S Y, Lai C Y, Huang J, et al. Molecular recognition inside of multifunctionalized mesoporous silicas:toward selective fluorescence detection of dopamine and glucosamine[J]. J Am Chem Soc, 2001,123(46):11510-11511.
[7] Lin V S, Radu D R, Han M K, et al. Oxidative polymerization of 1, 4-diethynylbenzene into highly conjugated poly(phenylene butadiynylene) within the channels of surface-functionalized mesoporous silica and alumina materials[J]. J Am Chem Soc, 2002,124(31):9040-9041.
[8] Li Y, Zhang H B, Huang W L, et al. Design and synthesis of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer[J]. Bioorg Med Chem Lett, 2008,18(12):3652-3655.
[9] Zhang Y, Zhou T, Duan J, et al. Inhibition of P-glycoprotein and Glutathione S-transferase-pi mediated resistance by fluoxetine in MCF-7/ADM cells[J]. Biomed Pharmacother, 2013,67(8):757-762.
[10] Wilczewska A Z, Niemirowicz K, Markiewicz K H, et al. Nanoparticles as drug delivery systems[J]. Pharmacol Rep, 2012,64(5):1020-1037.
[11] Mamaeva V, Sahlgren C, Lindén M. Mesoporous silica nanoparticles in medicine recent advances[J]. Adv Drug Deliv Rev, 2013,65(5):689-702.
[12] Wang W, Fang C, Wang X, et al. Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy[J]. Nanoscale, 2013,5(4):6249-6253.

巯嘌呤/维拉帕米-介孔氧化硅释药系统的构建及逆转耐药活性研究

6-Mercaptopurine/verapamil-mesoporous silica and reversing multidrug resistance

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