纳米金属有机骨架颗粒Hf-TCPP NMOFs用于肝癌CT成像的研究  

Hafnium-Tetra (4-carboxyphenyl) porphine nanoscale metal-organic frameworks (Hf-TCPP NMOFs) for Computed tomography of Liver Cancer

作　　者：张涛[1] 马冲[1] 朱坤[1] 姜志远 李晓燕[2] Zhang Tao;Ma Chong;Zhu Kun;Jiang Zhiyuan;Li Xiaoyan(Department of Gastrointestinal Colorectal and Anal Surgery,China-Japan Union Hospital of Jilin University,Changchun 130033,China;Department of Infection Control,Hospital of Stomatology,Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学中日联谊医院胃肠结直肠肛门外科,长春130033 [2]吉林大学口腔医院医院感染管理部,长春130021

出　　处：《中华实验外科杂志》2023年第6期1055-1058,共4页Chinese Journal of Experimental Surgery

基　　金：吉林省教育厅"十三五"科学技术项目(JJKH20190204KJ、JJKH20211143KJ、JJKH20201027KJ)。

摘　　要：目的:探索纳米金属有机骨架颗粒Hf-TCPP NMOFs用于肝癌CT成像的可行性。方法:应用微波辅助溶剂热技术制备纳米金属有机骨架颗粒Hf-TCPP NMOFs。通过人源HepG2细胞噻唑蓝(MTT)实验及BALB/c小鼠体内毒性试验验证Hf-TCPP NMOFs生物安全性。应用鼠源肝癌细胞Walk 256建立SD大鼠原位肝癌模型,通过原位肝癌CT成像探讨纳米金属有机骨架药物Hf-TCPP NMOFs用于肝癌CT造影剂的可行性及成像效果。组间比较采用t检验。结果:Hf-TCPP NMOFs粒径约120 nm,呈单分散的球形。细胞MTT试验表示超过80%HepG2细胞存活。通过注射3个不同药物浓度(10、20、40 mg/kg、对照组)药物后,检测小鼠不同时间点的血液生化指标。即使在最高浓度40 mg/kg时,第7天实验组与对照组比较,差异无统计学意义(WBC:8.14±0.23比8.17±0.26,t=-0.335,P>0.05;RBC:8.95±0.63比8.75±0.26,t=0.734,P>0.05;PLT:8.13±0.58比8.28±0.46,t=-0.617,P>0.05;LYM:2.21±0.28比2.24±0.15,t=-0.426,P>0.05;ALT:43.71±3.54比44.17±4.14,t=-0.531,P>0.05;AST:193.41±7.21比199.59±8.24,t=-1.032,P>0.05;CRE:35.13±2.72比36.86±3.19,t=-0.933,P>0.05;TBILI:0.97±0.15比0.99±0.16,t=-0.275,P>0.05;BUN:7.59±0.71比7.67±0.34,t=-0.251,P>0.05);第14天以下指标实验组与对照组比较差异无统计学意义(WBC:8.22±0.26比8.17±0.26,t=1.894,P>0.05;RBC:8.63±0.24比8.75±0.26,t=-0.517,P>0.05;PLT:8.14±0.48比8.28±0.46,t=-0.739,P>0.05;LYM:2.31±0.21比2.24±0.15,t=-0.926,P>0.05;ALT:44.54±6.65比44.17±4.14,t=0.236,P>0.05;TBILI:1.02±0.10比0.99±0.16,t=0.234,P>0.05;BUN:7.57±0.21比7.67±0.34,t=-0.317,P>0.05)。体重变化曲线显示注射不同浓度的小鼠体重随时间体重变化与对照组比较,虽然有所波动,但总体变化不大。重要器官(心、肝、脾、肺、肾)的组织病理学显示未见药物对脏器的损伤。SD大鼠原位肝癌模型体内CT成像效果表明Hf-TCPP NMOFs除了除具备较长的体内循环时间外,其在肝癌组织中表现出更佳的靶向聚集以及成�Objective Exploring the feasibility of Hafnium-Tetra(4-carboxyphenyl)porphine nanoscale metal-organic frameworks(Hf-TCPP NMOFs)for Computed tomography of liver cancer.Methods In this experiment,Hf-TCPP NMOFs were prepared by microwave-assisted solvothermal technique,and the biosafety of Hf-TCPP NMOFs was verified by MTT assay in human-derived HepG2 cells and in vivo toxicity test in BALB/c mice.We applied murine-derived hepatocellular carcinoma cells Walk 256 to establish an in situ hepatocellular carcinoma model in SD rats,andthen explored the feasibility and imaging effects of nanoscale metal-organic frameworks Hf-TCPP NMOFs for hepatocellular carcinoma CT contrast agent by in situ hepatocellular carcinoma CT imaging.Comparisonbetween groups was performed by t test.Results Hf-TCPP NMOFs have a particle size of about 120 nm and are monodisperse spherical in shape.The cell MTT test indicates that more than 80%of HepG2 cells are viable.After injecting three different drug concentrations(10,20,40 mg/kg,control group),the blood biochemical indexes of mice at different time points were detected.Even at the highest concentration of 40 mg/kg,there was no significant difference between the experimental group and the control group on day 7(WBC:8.14±0.23 vs.8.17±0.26,t=-0.335,P>0.05;RBC:8.95±0.63 vs.8.75±0.26,t=0.734,P>0.05;PLT:8.13±0.58 vs.8.28±0.46,t=-0.617,P>0.05;LYM:2.21±0.28 vs.2.24±0.15,t=-0.426,P>0.05;ALT:43.71±3.54 vs.44.17±4.14,t=-0.531,P>0.05;AST:193.41±7.21 vs.199.59±8.24,t=-1.032,P>0.05;CRE:35.13±2.72 vs.36.86±3.19,t=-0.933,P>0.05;TBILI:0.97±0.15 vs.0.99±0.16,t=-0.275,P>0.05;BUN:7.59±0.71 vs.7.67±0.34,t=-0.251,P>0.05);hematological analysis also showed no significant difference between the experimental group and the control groupon day 14 even at the highest concentration,and the difference was not statistically significant(WBC:8.22±0.26 vs.8.17±0.26,t=1.894,P>0.05;RBC:8.63±0.24 vs.8.75±0.26,t=-0.517,P>0.05;PLT:8.14±0.48 vs.8.28±0.46,t=-0.739,P>0.05;LYM:2.31±0.21 vs.2.24±0.15,t=-0.926

关 键 词：计算机断层扫描 肝癌 纳米金属有机骨架颗粒 

分 类 号：R735.7[医药卫生—肿瘤]