抗癌载药体系Fe3O4@ZIF-8@PA的合成及药物释放

doi:10.7503/cjcu20170176

摘要/Abstract

摘要：

采用溶剂热法合成磁性Fe₃O₄纳米粒子, 并以此为基底设计制备了一种具有pH响应核壳结构的磁性纳米复合材料Fe₃O₄@ZIF-8@PA. 该材料的比饱和磁化强度可达35.46 A·m²/g, 具有良好的磁性. Fe₃O₄纳米粒子呈球型结构, 分散性良好. 与基底相比, 复合微球的粒径尺寸明显增大, 但依然符合载体材料的理想尺寸且分布均匀. 此外, 载体具有多孔结构, 表面积较大, 载药效率和载药量分别高达96.4%和144.6 mg/g. 在pH为7.4和5.0的条件下对载药纳米粒子进行了药物释放研究. 24 h内, 粒子在2种pH下累计释放量分别为39.8%和78.6%. 通过药物缓释验证了载体的pH响应性能. 在实验中引入了对癌细胞具有杀伤作用的植酸, 使合成的载体具有一定的抗癌作用. 同时采用四甲基偶氮唑盐( MTT)法对人骨肉瘤细胞(MG-63)进行了体外分析实验, 证实材料与抗癌药物阿霉素(DOX)之间存在着一定的协同抗癌效果.

关键词: pH响应性, 协同作用, 磁性纳米复合材料, 核壳结构, 植酸, 药物释放

Abstract:

An anti-cancer and loading drug system was prepared. Fe₃O₄ nanopartiles prepared by hydrothermal method was chosen as substrate to design and fabricate pH responsive magnetic nanocomposites Fe₃O₄@ZIF-8@PA with core-shell structure. This nanomaterial exhibited high saturation of 35.46 A·m²/g and maintained well magnetic property. Fe₃O₄ nanopartiles showed spherical structure and good dispersion. Compared with the substrate, the particle size of composite microsphere increased significantly, but still conform to the ideal carrier material size. In addition, the carriers with porous structures showed large surface area, high drug loading efficiency and capacity for doxorubicin(DOX) of up to 96.4% and 144.6 mg/g. The drug release of nanopartiles loaded with drug was studied in pH=7.4 and 5.0. The total released percentage of two kinds of pH were 39.8% and 78.6%, respectively. The drug releasing experiment was also to perform to verify the constructed nanocarriers excellent pH-response. The introduction of phytic acid with inhibition to cancer cells made it possible that the carriers could kill tumor cells. The methyl thiazolyl tetrazolium(MTT) test act on human osteosarcoma cell line(MG-63) was also carried out in vitro to demonstrate the combination effect of anticancer between the carriers and DOX.

Key words: pH-responsiveness, Combination therapy, Magnetic nanocomposite, Core-shell structure, Phytic acid, Drug release

中图分类号:

O614
O636

TrendMD:

王晓丹, 徐丹丹, 吕维忠, 刘婧媛, 刘琦, 景晓燕, 王君. 抗癌载药体系Fe₃O₄@ZIF-8@PA的合成及药物释放. 高等学校化学学报, 2017, 38(11): 1927.

WANG Xiaodan, XU Dandan, LÜ Weizhong, LIU Jingyuan, LIU Qi, JING Xiaoyan, WANG Jun. Preparation and Drug Release of Anti-cancer Fe₃O₄@ZIF-8@PA System Loaded with Drug^†. Chem. J. Chinese Universities, 2017, 38(11): 1927.

图/表 9

Scheme 1 Schematic representation of basic constitution of Fe3O4@ZIF-8@PA nanoparticles, loading and multi-responsive releasing of DOX and the nanocarriers combining with DOX acting in MG-63 cells

Fig.1 SEM images(A—C)and TEM images(D—F) of Fe3O4(A, D), Fe3O4@ZIF-8(B, E) and Fe3O4@ZIF-8@PA(C, F) nanoparticlesInset of (F) is particle size distribution curve of Fe3O4@ZIF-8@PA.

Fig.2 FTIR spectra of pure ZIF-8(a), Fe3O4@ZIF-8(b), Fe3O4@ZIF-8@PA(c), PA(d) and Fe3O4(e)

Fig.3 XRD patterns of pure ZI F-8(a), Fe3O4@ZIF-8(b), Fe3O4@ZIF-8@PA(c) and Fe3O4(d)

Fig.4 TG curves of ZIF-8(a) and Fe3O4@ZIF-8@PA(b) nanoparticles

Fig.5 Nitrogen adsorption-desorption isotherm with pore size distribution curves in the inset of Fe3O4@ZIF-8(A) and Fe3O4@ZIF-8@PA(B)

Fig.6 Magnetic hysteresis curves of Fe3O4@ZIF-8@PA(a), Fe3O4@ZIF-8(b) and Fe3O4(c)Inset: magnetic separation experiment.

Fig.7 Absorbance spectra of bare Fe3O4@ZIF-8@PA nanocarriers(a), Fe3O4@ZIF-8@PA-DOX(b) and free DOX(c)(A) and release of DOX from Fe3O4@ZIF-8@PA-DOX in buffer solutions at pH=7.4(a) and 5.0(b)(B)

Fig.8 Cell viabilities of pure DOX, Fe3O4@ZIF-8@PA-DOX, Fe3O4@ZIF-8@PA and Fe3O4@ZIF-8 with the same concentration(A) and pure DOX and Fe3O4@ZIF-8@PA-DOX nanoparticles with different concentrations to MG-63 cells examined by MTT assay(B)

参考文献 27

[1]	Holohan C., Van Schaeybroeck S., Longley D. B., Johnston P. G., Chem. J. Chinese Universities,2010, 31(10), 714-726
[2]	Wang Y., Wang X. Y., Lü Y. Y., Xu W. B., Guo Y., Xu L., Chem. J. Chinese Universities,2010, 31(12), 2866-2870
	(王岩, 王笑英, 吕言云, 许文彬, 郭轶, 徐力. 高等学校化学学报, 2013, 34(12), 2866-2870)
[3]	Zhao Y. B., Qiu Z. M., Huang J. Y., Chinese. J. Chem. Eng., 2008, 16(3), 451-455
	(赵原壁, 邱祖民, 黄佳英. 中国化学工程学报, 2008, 16(3), 451-455)
[4]	Pan D. K., Zhang H., Chem. J. Chinese Universities,2010, 31(69), 1545-1552
	(盘登科, 张慧. 化学学报, 2011, 13(69), 1545-1552)
[5]	He M., Zhou J., Chen J., Zheng F., Wang D., Shi R., Guo Z., Wang H., Chen Q., Chem. J. Chinese Universities,2010, 31(46), 9033-9042
[6]	Qiao Z. W., Li L. B., Zhou J., Chem. J. Chinese Universities,2010, 31(12), 2638-2644
	(乔智威, 李理波, 周健. 高等学校化学学报, 2014, 35(12), 2638-2644)
[7]	You B., Xing W. T., Wu L. M., Chem. J. Chinese Universities,2010, 31(12), 2408-2412
	(游波, 邢文涛, 武利民. 高等学校化学学报, 2007, 28(12), 2408-2412)
[8]	Shears S. B., Cellular Signallin., 2001, 13(3), 151-158
[9]	Sun K. H., Liu Z., Liu C. J., Yu T., Shang T., Huang C., Zhou M., Liu C., Ran F., Li Y., Shi Y., Pan L. J., Chem. J. Chinese Universities,2010, 31, 23931-23942
[10]	Graf E., Eaton J. W., Cancer,1985, 56(4), 717-718
[11]	Shamsuddin A. M., Int. J. Food Sci. Tech., 2002, 37(7), 769-782
[12]	Xu D. D., Xie R., Xu T. Y., Guo X. J., Liu Q., Liu J. Y., Lv W. Z., Jing X. Y., Zhang H. S., Wang J., Chem. J. Chinese Universities,2010, 31(91), 88248-88254
[13]	Hu Y., Kazemian H., Rohani S., Huang Y. N., Song Y., Chem. Commun., 2011, 47(47), 12694-12696
[14]	Zhu Y., Liu Q., Caro J., Huang A.,Separation and Purification Technology, 2015, 146, 68-74
[15]	Ren H., Zhang L., An J. P., Wang T. T., Li L., Si X. Y., He L., Wu X. T., Wang C. G., Su Z. M., Chem. Commun., 2014, 50(8), 1000-1002
[16]	Sjoeberg B. M., Sanders-Loehr J., Loehr T. M., Biochemistry,1987, 26(14), 4242-4247
[17]	Xiang J., Shen X. Q., Zhu Y. W., Inorg. Mater., 2008, 5(23), 1006-1010
	(向军, 沈湘黔, 朱永伟. 无机材料学报, 2008, 5(23), 1006-1010)
[18]	Hazarika P., Gogoi P., Hatibaruah S., Konwar D., Green Chemistry Letters and Reviews,2011, 4(4), 327-339
[19]	Kannan S., Ferreira J. M. F., Chem. Mater., 2006, 18(1), 198-203
[20]	Kang X. J., Dai Y. L., Ma P. A., Y D. M., Li C. X., Hou Z. Y., Cheng Z. Y., Lin J., Chem. Eur. J., 2012, 18(49), 15676-15682
[21]	Jiao H., Yang H. Q., Song Y. Z., Wu X. Y., Chen D. C., Wang M. Z., Chem. J. Chinese Universities,2010, 31(65), 2336-2342
	(焦华, 杨合情, 宋玉哲, 武小燕, 陈迪春, 王明珍. 化学学报, 2007, 20(65), 2336-2342)
[22]	Chumee J., Grisdanurak N., Neramittagapong S., Wittayakun J., Braz. J. Chem. Eng., 2009, 26(2), 367-373
[23]	Zheng J., Cheng C., Fang W. J., Chen C., Yan R. W., Huai H. X., Wang C. C., Cryst. Eng. Comm., 2014, 16(19), 3960-3964
[24]	Zhang S., Zhou Y., Nie W., Song L., Cellulose,2012, 19(6), 2081-2091
[25]	Liu J., Huang Y. R., Kumar A., Tan A., Jin S. B., Mozhi A., Liang X. J., Biotechnol. Adv., 2014, 32, 693-710
[26]	Yang B.H., Zhao W. O., Li C. J., Li Y. P., Wang J. Y.,Acta Polym. Sin., 2014, (5), 636-642
	(杨伯涵, 赵外鸥, 李采金, 李亚鹏, 王静媛. 高分子学报, 2014, (5), 636-642)
[27]	Saisyo A., Nakamura H., Fang J., Tsukigawa K., Greish K., Furukawa H., Maeda H., Colloids and Chem. J. Chinese Universities,2010, 31, 128-137

抗癌载药体系Fe₃O₄@ZIF-8@PA的合成及药物释放

Preparation and Drug Release of Anti-cancer Fe₃O₄@ZIF-8@PA System Loaded with Drug^†

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 9

参考文献 27

相关文章 15

编辑推荐

Metrics

本文评价

[1]	樊晓慧, 汪洋, 杨园园, 张玉红. pH/酶/光热多重响应的金纳米笼/透明质酸核壳结构纳米载体的制备与性能[J]. 高等学校化学学报, 2022, 43(4): 20210855.
[2]	郭彪, 赵晨灿, 刘芯辛, 于洲, 周丽景, 袁宏明, 赵震. 表面水热碳层对磁性NiFe₂O₄八面体光催化活性的影响[J]. 高等学校化学学报, 2022, 43(11): 20220472.
[3]	陶幸福, 韩成龙, 杨扬, 刘堃. 铝纳米粒子表面引发聚合制备核壳纳米结构[J]. 高等学校化学学报, 2022, 43(10): 20220367.
[4]	韩一秀, 吴殿国, 李宏谱, 殷鸿尧, 梅拥军, 冯玉军, 钟祖勤. 低温非水环境中疏水缔合聚丙烯酸钠与两性离子表面活性剂的相互作用[J]. 高等学校化学学报, 2021, 42(6): 2056.
[5]	孙涛, 王一波. 柱芳烃与烷烃间C―H…π和C―H…O的作用本质及协同性[J]. 高等学校化学学报, 2020, 41(9): 2046.
[6]	贾雪梅, 程铁欣, 周广栋. 沥青质及其亚组分与烷基苯磺酸盐溶液在降低界面张力中的协同作用[J]. 高等学校化学学报, 2020, 41(7): 1631.
[7]	赵鹏,张晋腾,林艳红. Mg-ZnO复合物的紫外光催化效率及协同作用研究[J]. 高等学校化学学报, 2020, 41(3): 538.
[8]	蒋静,陈晓丽,黄亚励,张奇龙,徐红,杨小生. 八元瓜环与常山碱的相互作用模式[J]. 高等学校化学学报, 2020, 41(2): 277.
[9]	易江, 秦兴美, 陈飞武. 二元和三元复合物中阳离子硫键与磷键的理论研究[J]. 高等学校化学学报, 2019, 40(7): 1439.
[10]	朱钦富, 胡可珍, 李小杰, 陈明清. pH响应性树枝状聚合物-金纳米粒子复合药物载体的制备[J]. 高等学校化学学报, 2019, 40(5): 1065.
[11]	田龙,龙艳,宋术岩,王成. 花状结构Mn/CuO-CeO₂的合成及对CO氧化反应的催化性能[J]. 高等学校化学学报, 2019, 40(12): 2549.
[12]	方超, 朱焓毓, 刘晔, 赵外欧, 李亚鹏, 王静媛. 过氧化氢敏感的靶向荧光载药纳米粒子的制备及在动脉粥样硬化中的应用[J]. 高等学校化学学报, 2018, 39(9): 2071.
[13]	黄薇薇, 任家旺, 方千荣, VALTCHEV Valentin. 核壳结构分子筛β@IISERP-COF2小球的合成[J]. 高等学校化学学报, 2018, 39(6): 1127.
[14]	叶慧, 刘亚博, 贾玉玺. 弱聚电解质水凝胶溶胀释药的数值模拟[J]. 高等学校化学学报, 2018, 39(4): 817.
[15]	宋文植, 李慧, 张艳, 何丹, 李英姿, 黄臻臻, 刘新, 尹万忠. 具有近红外光热转换性能的双层氧化硅包覆金纳米花复合材料的制备及体内代谢研究[J]. 高等学校化学学报, 2018, 39(12): 2644.