中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2014年
2期
85-91
,共7页
单秀红%袁德琪%熊非%顾宁%王鹏
單秀紅%袁德琪%熊非%顧寧%王鵬
단수홍%원덕기%웅비%고저%왕붕
肿瘤%2-脱氧-D-葡萄糖%纳米粒子%磁共振成像%小鼠,裸
腫瘤%2-脫氧-D-葡萄糖%納米粒子%磁共振成像%小鼠,裸
종류%2-탈양-D-포도당%납미입자%자공진성상%소서,라
Neoplasms%2-deoxy-D-glucose%Nanoparticles%Magnetic resonance imaging%Nude mice
目的 探讨2-脱氧-D-葡萄糖(2-DG)标记的氧化铁纳米粒子γ-Fe2O3@DMSA-DG NPs作为磁共振成像(MRI)对比剂检测肿瘤的功能.方法 制备γ-Fe2O3@DMSA-DG NPs纳米粒子.采用普鲁士蓝染色、比色法、MRI T2WI及多回波序列检测A549细胞靶向吸收γ-Fe2O3@DMSA-DG NPs的情况,以γ-Fe2O3@DMSA NPs作为对照剂,游离D-葡萄糖作为竞争性抑制剂.制备A549细胞荷瘤裸鼠,并经尾静脉注射γ-Fe2O3@DMSA-DG NPs或γ-Fe2O3@DMSA NPs冻干粉的无菌水悬液,注射前和注射后6、12、24、48 h进行MRI检查,测量肿瘤组织、脑组织、肝组织及大腿部骨骼肌的T2信号强度和肿瘤组织的T2值.结果 γ-Fe2O3@DMSA NPs和γ-Fe2O3@DMSA-DG NPs粒径无明显差异,平均粒径约为10 nm.红外光谱图显示,γ-Fe2O3@DMSA-DG NPs表面有C-N伸缩振动峰,表明2-DG成功标记到γ-Fe2O3@DMSA NPs的表面.普鲁士蓝染色、比色法、MRI T2WI及多回波序列检测显示,生长高峰期的A549细胞在2h内吸收γ-Fe2O3@DMSA-DG NPs明显多于γ-Fe2 O3@DMSA NPs,而且吸收的γ-Fe2O3@DMSA-DG NPs能够被游离D-葡萄糖有效抑制.体内实验显示,实验组荷瘤裸鼠在-Fe2O3@DMSA-DG NPs注射前和注射后6、12、24、48 h,肿瘤组织的T2信号强度分别为(326.00±16.26)s、(276.40±5.13)s、(268.40±30.58)s、(240.40±25.93)s和(262.20±30.04)s,肿瘤组织的T2值分别为(735.80±20.93)ms、(645.80±69.58)ms、(615.00±124.61)ms、(570.60±67.78) ms和(537.80±105.29) ms;而对照组荷瘤裸鼠在γ-Fe2 O3@DMSA NPs注射前和注射后6、12、24、48 h,肿瘤组织的T2信号强度分别为(335.60±4.93)s、(290.80±5.93)s、(273.40±15.08)s、(327.40±16.65)s和(313.20±20.45)s,肿瘤组织的T2值分别为(686.00±21.44) ms、(617.80±69.93) ms、(645.20±85.89) ms、(669.40±13.72) ms和(608.80±61.90)ms.注射γ-Fe2O3@DMSA-DG NPs或γ-Fe2O3@DMSA NPs的荷瘤裸鼠,其肝脏信号强度均有明显下降,脑组织及骨骼肌信号强度无明显变化.结论 γ-Fe2O3@DMSA-DG NPs有靶向肿瘤过表达葡萄糖受体的功能,可作为靶向肿瘤的MRI对比剂.
目的 探討2-脫氧-D-葡萄糖(2-DG)標記的氧化鐵納米粒子γ-Fe2O3@DMSA-DG NPs作為磁共振成像(MRI)對比劑檢測腫瘤的功能.方法 製備γ-Fe2O3@DMSA-DG NPs納米粒子.採用普魯士藍染色、比色法、MRI T2WI及多迴波序列檢測A549細胞靶嚮吸收γ-Fe2O3@DMSA-DG NPs的情況,以γ-Fe2O3@DMSA NPs作為對照劑,遊離D-葡萄糖作為競爭性抑製劑.製備A549細胞荷瘤裸鼠,併經尾靜脈註射γ-Fe2O3@DMSA-DG NPs或γ-Fe2O3@DMSA NPs凍榦粉的無菌水懸液,註射前和註射後6、12、24、48 h進行MRI檢查,測量腫瘤組織、腦組織、肝組織及大腿部骨骼肌的T2信號彊度和腫瘤組織的T2值.結果 γ-Fe2O3@DMSA NPs和γ-Fe2O3@DMSA-DG NPs粒徑無明顯差異,平均粒徑約為10 nm.紅外光譜圖顯示,γ-Fe2O3@DMSA-DG NPs錶麵有C-N伸縮振動峰,錶明2-DG成功標記到γ-Fe2O3@DMSA NPs的錶麵.普魯士藍染色、比色法、MRI T2WI及多迴波序列檢測顯示,生長高峰期的A549細胞在2h內吸收γ-Fe2O3@DMSA-DG NPs明顯多于γ-Fe2 O3@DMSA NPs,而且吸收的γ-Fe2O3@DMSA-DG NPs能夠被遊離D-葡萄糖有效抑製.體內實驗顯示,實驗組荷瘤裸鼠在-Fe2O3@DMSA-DG NPs註射前和註射後6、12、24、48 h,腫瘤組織的T2信號彊度分彆為(326.00±16.26)s、(276.40±5.13)s、(268.40±30.58)s、(240.40±25.93)s和(262.20±30.04)s,腫瘤組織的T2值分彆為(735.80±20.93)ms、(645.80±69.58)ms、(615.00±124.61)ms、(570.60±67.78) ms和(537.80±105.29) ms;而對照組荷瘤裸鼠在γ-Fe2 O3@DMSA NPs註射前和註射後6、12、24、48 h,腫瘤組織的T2信號彊度分彆為(335.60±4.93)s、(290.80±5.93)s、(273.40±15.08)s、(327.40±16.65)s和(313.20±20.45)s,腫瘤組織的T2值分彆為(686.00±21.44) ms、(617.80±69.93) ms、(645.20±85.89) ms、(669.40±13.72) ms和(608.80±61.90)ms.註射γ-Fe2O3@DMSA-DG NPs或γ-Fe2O3@DMSA NPs的荷瘤裸鼠,其肝髒信號彊度均有明顯下降,腦組織及骨骼肌信號彊度無明顯變化.結論 γ-Fe2O3@DMSA-DG NPs有靶嚮腫瘤過錶達葡萄糖受體的功能,可作為靶嚮腫瘤的MRI對比劑.
목적 탐토2-탈양-D-포도당(2-DG)표기적양화철납미입자γ-Fe2O3@DMSA-DG NPs작위자공진성상(MRI)대비제검측종류적공능.방법 제비γ-Fe2O3@DMSA-DG NPs납미입자.채용보로사람염색、비색법、MRI T2WI급다회파서렬검측A549세포파향흡수γ-Fe2O3@DMSA-DG NPs적정황,이γ-Fe2O3@DMSA NPs작위대조제,유리D-포도당작위경쟁성억제제.제비A549세포하류라서,병경미정맥주사γ-Fe2O3@DMSA-DG NPs혹γ-Fe2O3@DMSA NPs동간분적무균수현액,주사전화주사후6、12、24、48 h진행MRI검사,측량종류조직、뇌조직、간조직급대퇴부골격기적T2신호강도화종류조직적T2치.결과 γ-Fe2O3@DMSA NPs화γ-Fe2O3@DMSA-DG NPs립경무명현차이,평균립경약위10 nm.홍외광보도현시,γ-Fe2O3@DMSA-DG NPs표면유C-N신축진동봉,표명2-DG성공표기도γ-Fe2O3@DMSA NPs적표면.보로사람염색、비색법、MRI T2WI급다회파서렬검측현시,생장고봉기적A549세포재2h내흡수γ-Fe2O3@DMSA-DG NPs명현다우γ-Fe2 O3@DMSA NPs,이차흡수적γ-Fe2O3@DMSA-DG NPs능구피유리D-포도당유효억제.체내실험현시,실험조하류라서재-Fe2O3@DMSA-DG NPs주사전화주사후6、12、24、48 h,종류조직적T2신호강도분별위(326.00±16.26)s、(276.40±5.13)s、(268.40±30.58)s、(240.40±25.93)s화(262.20±30.04)s,종류조직적T2치분별위(735.80±20.93)ms、(645.80±69.58)ms、(615.00±124.61)ms、(570.60±67.78) ms화(537.80±105.29) ms;이대조조하류라서재γ-Fe2 O3@DMSA NPs주사전화주사후6、12、24、48 h,종류조직적T2신호강도분별위(335.60±4.93)s、(290.80±5.93)s、(273.40±15.08)s、(327.40±16.65)s화(313.20±20.45)s,종류조직적T2치분별위(686.00±21.44) ms、(617.80±69.93) ms、(645.20±85.89) ms、(669.40±13.72) ms화(608.80±61.90)ms.주사γ-Fe2O3@DMSA-DG NPs혹γ-Fe2O3@DMSA NPs적하류라서,기간장신호강도균유명현하강,뇌조직급골격기신호강도무명현변화.결론 γ-Fe2O3@DMSA-DG NPs유파향종류과표체포도당수체적공능,가작위파향종류적MRI대비제.
Objective To evaluate the role of 2-deoxy-D-glucose (2-DG) modified supermagnetic iron oxide nanoparticles (SPIO) (γ-Fe2O3@DMSA-DG NPs) in tumor detection as a magnetic resonance imaging (MRI) contrast agent.Methods γ-Fe2O3@DMSA-DG NPs was prepared.The degree of A549 cells targeted absorption of γ-Fe2O3@DMSA-DG NPs was detected by Prussian blue staining,colorimetric assay,T2W and multi-echo sequence MRI.γ-Fe2O3@DMSA NPs was used as a control agent,and free D-glucose as a competitive inhibitor.Human lung adenocarcinoma A549 xenograft tumor was prepared in nude mice.Sterile aqueous suspension of γ-Fe2O3@DMSA NPs or γ-Fe2O3@DMSA-DG NPs was injected into the tail vein of nude mice.Before and 6,12,24,48 h after injection,MRI imaging of the mice was performed.T2 signal intensity of the tumor,brain,liver and thigh skeletal muscles,and T2 values of the tumors were measured.Results The average diameter of the particles was about 10 nm,and there were no significant differences between the diameters of γ-Fe2O3@DMSA NPs and γ-Fe2O3@DMSA-DG NPs.The IR spectra showed the C-N retractable vibration peak at γ-Fe2O3@DMSA-DG NPs surface,indicating that 2-DG was conjugated to the γ-Fe2O3@DMSA NPs.The Prussian blue staining,colorimetric assay,MRI T2 signal intensity and T2 values revealed that γ-Fe2O3@DMSA-DG NPs were significantly more absorbed by A549 cells at growth peak than γ-Fe2O3@DMSA NPs,and the absorption of γ-Fe2O3@DMSA-DG NP was inhibited by free D-glucose.The results of in vivo examination showed that before and at 6,12,24,48 h after injection of γ-Fe2O3@DMSA-DG NPs,the mean T2 signal intensities of the tumors were (326.00 ±16.26)s,(276.40 ±5.13)s,(268.40±30.58)s,(240.40 ±25.93)s,(262.20±30.04)s,respectively,and the T2 values of the tumors were (735.80 ± 20.93) ms,(645.80 ± 69.58) ms,(615.00 ±124.61) ms,(570.60 ± 67.78) ms,and (537.80 ± 105.29) ms,respectively.However,before and at 6,12,24,48 h after injection of γ-Fe2O3@DMSA NPs,the mean T2 signal intensities of the tumors were (335.60±4.93)s,(290.80±5.93)s,(273.4O±15.08)s,(327.40 ±16.65)s,and (313.20 ±20.45)s,respectively,and T2 values were (686.00 ± 21.44) ms,(617.80 ± 69.93) ms,(645.20 ± 85.89) ms,(669.40 ± 13.72) ms,and (608.80 ± 61.90) ms,respectively.The T2 signal intensity and T2 value of the tumors were not declined generally after injection.The liver T2 signal intensity was decreased after injection of both γ-Fe2O3@DMSA-DG NPs and γ-Fe2O3@DMSA NPs,and T2 signal intensity of the brain and muscle did not show significant changes.Conclusions γ-Fe2O3@DMSA-DG NPs has an ability to target glucose receptors overexpressed in tumors,and may serve as a MRI contrast agent for tumor detection.