抗癌载药体系Fe_3O_4@ZIF-8@PA的合成及药物释放
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摘要
采用溶剂热法合成磁性Fe_3O_4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Fe_3O_4@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.Fe_3O_4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.
An anti-cancer and loading drug system was prepared. Fe_3O_4 nanopartiles prepared by hydrothermal method was chosen as substrate to design and fabricate pH responsive magnetic nanocomposites Fe_3O_4@ZIF-8@PA with core-shell structure. This nanomaterial exhibited high saturation of 35. 46 A·m2/g and maintained well magnetic property. Fe_3O_4 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.
An anti-cancer and loading drug system was prepared. Fe_3O_4 nanopartiles prepared by hydrothermal method was chosen as substrate to design and fabricate pH responsive magnetic nanocomposites Fe_3O_4@ZIF-8@PA with core-shell structure. This nanomaterial exhibited high saturation of 35. 46 A·m2/g and maintained well magnetic property. Fe_3O_4 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.
引文
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[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.,Acta Chim.Sinica,2011,13(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.,J.Mater.Chem.B,2015,3(46),9033—9042
[6]Qiao Z.W.,Li L.B.,Zhou J.,Chem.J.Chinese Universities,2014,35(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,2007,28(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 Signalling,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.,Scientific Reports,2016,6,23931—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.,RSC Advances,2016,6(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.,Acta Chim.Sinica,2007,20(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 Surfaces B:Biointerfaces,2016,138,128—137