UIO-66(Zr)对人正常肝细胞L02的安全性评价
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摘要
目的观察以锆为基础的金属有机骨架材料——UIO-66(Zr)对人正常肝细胞L02的作用,初步探究其生物相容性及安全性。方法采用MTT法和LDH漏出率检测法评价UIO-66(Zr)对L02细胞的损伤程度;利用DAPI染色法观察细胞核形态;用AnnexinⅤ-FITC法观察细胞凋亡情况。结果低浓度下,UIO-66(Zr)具有较好的细胞安全性;高浓度(≥40μg·mL~(-1))的UIO-66(Zr)能破坏细胞膜,诱导细胞凋亡,抑制L02细胞增殖,显示出一定细胞毒性。结论 UIO-66(Zr)的IC50为52.22mg·mL~(-1),体外生物安全浓度小于40μg·mL~(-1)。
Objective To determine the biocompatibility and safety of UIO-66(Zr) by analyzing of the effect of UIO-66(Zr) on L02 cells since metal organic frameworks(MOFs) has been widely used as drug carriers in medicine. Methods MTT method and LDH release assay were used to test the degree of L02 cell injury affected by UIO-66(Zr). Nuclear morphological and cell apoptosis were observed by DAPI staining and Annexin Ⅴ FITC/PI staining. Results UIO-66(Zr) had better cell safty at low concentrations. The increase of UIO-66(Zr) dosage, increased the content release of LDH, raised apoptotic rate and inhibited cell proliferation at high concentration( ≥ 40 μg·mL~(-1)). Conclusion IC50 of UIO-66(Zr) is 52.22 mg·mL~(-1) in L02 cells and its biosafety concentration is 40 μg·mL~(-1) in vitro.
Objective To determine the biocompatibility and safety of UIO-66(Zr) by analyzing of the effect of UIO-66(Zr) on L02 cells since metal organic frameworks(MOFs) has been widely used as drug carriers in medicine. Methods MTT method and LDH release assay were used to test the degree of L02 cell injury affected by UIO-66(Zr). Nuclear morphological and cell apoptosis were observed by DAPI staining and Annexin Ⅴ FITC/PI staining. Results UIO-66(Zr) had better cell safty at low concentrations. The increase of UIO-66(Zr) dosage, increased the content release of LDH, raised apoptotic rate and inhibited cell proliferation at high concentration( ≥ 40 μg·mL~(-1)). Conclusion IC50 of UIO-66(Zr) is 52.22 mg·mL~(-1) in L02 cells and its biosafety concentration is 40 μg·mL~(-1) in vitro.
引文
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[17]孙悦,刘嘉褀,王路,等.纳米二氧化硅对A549细胞的毒性作用[J].环境与职业医学,2017,34(6):536-541.
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[20]Lin S,Liu X,Tan L,et al.Porous Iron-carboxylate metal-organic framework:a novel bioplatform with sustained antibacterial efficacy and nontoxicity[J].ACS Appl Mater Inte,2017,9(22):19248-19252.
[21]孙悦,刘嘉褀,王路,等.纳米二氧化硅对A549细胞的毒性作用[J].环境与职业医学,2017,34(6):536-541.
[2]Beg S,Rahman M,Jain A,et al.Nanoporous metal organic frameworks as hybrid polymer–metal composites for drug delivery and biomedical applications[J].Drug Discov Today,2017,22(4):625-637.
[3]李玉晨.荧光成像与药物控释双功能MOFs材料的制备与应用[D].哈尔滨:哈尔滨工业大学,2014.
[4]王洁莹.金属有机骨架材料的合成及其负载5-氟尿嘧啶的性质研究[D].沈阳:沈阳师范大学,2017.
[5]王可可,刘大欢,仲崇立.一种基于含甲基的噻吩型配体和锆的超稳定金属-有机骨架材料[A]//第18届全国分子筛学术大会论文集(下)[C].中国化学会分子筛专业委员会,2015.
[6]Bai Y,Dou YB,Xie LH,et al.Zr-based metal-organic frameworks:design,synthesis,structure,and applications[J].Chem Soc Rev,2016,45(8):2327-2367.
[7]杜峰,李鹂.Ui O-66(Zr)系列MOFs催化材料的制备及在乳酸乙酯合成中的应用[J].化工进展,2015,34(11):3938-3943.
[8]刘强.金属有机骨架材料Ui O-66的制备及表征[J].云南化工,2016,43(6):1-7.
[9]Dong Y,Zhang H,Lei F,et al.Benzimidazole-functionalized Zr-Ui O-66 nanocrystals for luminescent sensing of Fe3+,in water[J].J Solid State Chem,2016,245:160-163.
[10]Ding J,Yang Z,He C,et al.Ui O-66(Zr)coupled with Bi2Mo O6 as photocatalyst for visible-light promoted dye degradation[J].J Colloid Interface Sci,2017,497:126-133.
[11]Yang F,Li WY,Tang BH.Facile synthesis of amorphous Ui O-66(Zr-MOF)for supercapacitor application[J].J Alloy Compd,2018,733:8-14.
[12]Filippousi M,Turner S,Leus K,et al.Biocompatible Zr-based nanoscale MOFs coated with modified poly(ε-caprolactone)as anticancer drug carriers[J].Int J Pharm,2016,509(1-2):208-218.
[13]Mozhgan A,Mostafa Z,Hossein M,et al.Preparation of metal-organic frameworks Ui O-66 for adsorptive re-moval of methotrexate from aqueous solution[J].J Inorg Organomet,2018,28(1):177-186.
[14]Lázaro IA,Haddad S,Sacca S,et al.Selective surface PEGylation of Ui O-66 nanoparticles for enhanced stability,cell uptake,and p H-responsive drug delivery[J].Chem,2017,2(4):561-578.
[15]Tan LL,Song N,Zhang XA,et al.Ca2+,p H and thermo triple-responsive mechanized Zr-based MOFs for on-command drug release in bone diseases[J].J Mater Chem B,2015,4(1):135-140.
[16]马凤森,喻炎,章捷,等.生物材料细胞毒性评价研究进展[J].材料导报,2018,32(1):76-85.
[17]孙悦,刘嘉褀,王路,等.纳米二氧化硅对A549细胞的毒性作用[J].环境与职业医学,2017,34(6):536-541.
[18]张艳芳,金婵,马春旺,等.几种纳米材料细胞毒性效应的研究现状[J].第二军医大学学报,2010,31(11):1234-1238.
[19]杨勇骥,汤莹,于洋,等.纳米材料侵入细胞的电镜研究[J].电子显微学报,2008,27(5):400-403.
[20]Lin S,Liu X,Tan L,et al.Porous Iron-carboxylate metal-organic framework:a novel bioplatform with sustained antibacterial efficacy and nontoxicity[J].ACS Appl Mater Inte,2017,9(22):19248-19252.
[21]孙悦,刘嘉褀,王路,等.纳米二氧化硅对A549细胞的毒性作用[J].环境与职业医学,2017,34(6):536-541.