摘要
目的合成一种靶向整合素αvβ3的新型MRI及近红外荧光双模态分子探针,并初步研究其表征、MRI表现及体内MRI/近红外荧光双模态成像的可能性。方法采用双乳化法将Fe_(3)O_(4)磁性纳米颗粒和Cy5.5荧光染料共同包裹于聚乳酸羟基乙酸[poly(D,L-lactic-co-glycolicacid),PLGA]中,制备PLGA-Cy5.5-@Fe_(3)O_(4)纳米球,再将整合素αvβ3的靶向配体精氨酸-甘氨酸-天冬氨酸多肽环序列(cRGD)偶联到PLGA-Cy5.5-@Fe_(3)O_(4)纳米球的表面,得到双模态分子探针PLGA-Cy5.5-@Fe_(3)O_(4)-RGD。之后利用动态光散射法(DLS)检测其水合粒径及Zeta电位,红外分析(FTIR)测定其红外光谱;运用荧光光谱仪测得其荧光光谱;激光共聚焦显微镜检测乳腺癌细胞表明整合素αvβ3的表达;MRI观察其探针的体外MRI成像;皮下乳腺癌模型裸鼠尾静脉注射探针,分别进行体内MRI及近红外荧光成像,评价探针的双模态成像性能,扫描后对裸鼠进行解剖,取组织病理切片行HE染色。结果PLGA-Cy5.5-@Fe_(3)O_(4)-RGD制备成功,测得其水动力尺寸为(212.3±44.62)nm,Zeta电位为(-21.3±5.57)mV,在紫外线波长701 nm处有最大吸收峰;随着分子探针浓度的逐渐升高,T_(2)信号逐步降低,图像由白到黑;激光共聚焦扫描显微镜验证了整合素αvβ3主要表达于细胞质和细胞膜表面;于皮下乳腺癌模型裸鼠体内注射PLGA-Cy5.5-@Fe_(3)O_(4)-RGD后进行磁共振T_(2)WI和荧光成像,在注射2 h内肿瘤部位的T_(2)WI信号逐渐降低,而其荧光强度逐渐升高。结论PLGA-Cy5.5-@Fe_(3)O_(4)-RGD双模态分子探针具有良好的稳定性、分散性,且能作为双模态显像剂用于荧光及MRI成像。
Objective A novel dual-mode molecular probe targeting integrinαvβ3 by magnetic resonance imaging(MRI)and near infrared(NIR)fluorescence imaging was synthesized,and its characterization,MRI performance and the possibility of dual-mode imaging of MRI/NIR in vivowere studied.Methods Fe_(3)O_(4) magnetic nanoparticles and Cy5.5 fluorescent dye were encapsulated in poly(D,L-lactic-co-glycolicacid)(PLGA)by double emulsification method to prepare PLGA-Cy5.5-@Fe_(3)O_(4) nanospheres,and then arginine-glycine-aspartic acid polypeptide ring sequence(cRGD),which is the target ligand of integrinαvβ3,was coupled to the surface of PLGA-Cy5.5-@Fe_(3)O_(4) nanospheres.The dual-mode molecular probe PLGA-Cy5.5-@Fe_(3)O_(4)-RGD was obtained.After that,the hydrated particle size and Zeta potential were detected by dynamic light scattering(DLS),the infrared spectrum was measured by infrared analysis(FTIR),the fluorescence spectrum was measured by fluorescence spectrometer,the expression of integrinαvβ3 was detected by laser confocal microscope,and the in vitro MR imaging of the probe was observed by MRI.The probe was injected into the tail vein of the subcutaneous breast cancer model in nude mice,and the MRI and NIR images were performed in vivo.The dual-mode imaging performance of the probe was evaluated.After scanning,the nude mice were dissected,and the histopathological sections were stained with HE.Results PLGA-Cy5.5-@Fe_(3)O_(4)-RGD was successfully prepared and its hydrodynamic size was(212.3±44.62)nm.The Zeta potential was(-21.3±5.57)MV and there was a maximum absorption peak at ultraviolet wavelength 701 nm.With the increase of molecular probe concentration,the T_(2) signal decreased gradually,the image changed from white to black.Confocal laser scanning microscope confirmed that integrinαvβ3 was mainly expressed on the surface of cytoplasm and cell membrane.After injection of PLGA-Cy5.5-@Fe_(3)O_(4)-RGD into subcutaneous breast cancer model nude mice underwent magnetic resonance T_(2)-weighted imaging and fluoresc
作者
张毓
聂贞慧
曾馨逸
廖海
苏丹柯
ZHANG Yu;NIE Zhenhui;ZENG Xinyi(Department of Radiology,Medical Imaging Center,Cancer Hospital Affiliated to Guangxi Medical University,Nanning 530021,P.R.China)
出处
《临床放射学杂志》
北大核心
2021年第6期1221-1226,共6页
Journal of Clinical Radiology
基金
国家自然科学基金项目(编号:81760517)。
关键词
双模态探针
整合素ΑVΒ3
磁共振成像
荧光成像
The double modal probe
Integrinαvβ3
Magnetic resonance imaging
Fluorescence imaging
