超顺磁氧化铁纳米微粒在HER-2阳性乳腺癌模型MRI和荧光成像中的应用

Application of superparamagnetic iron oxide nanoparticles in MRI and fluorescence imaging of HER-2 positive breast cancer model

目的分析超顺磁氧化铁纳米微粒(SPIONs)在人表皮生长因子受体2(HER-2)阳性乳腺癌模型磁共振成像(MRI)和荧光成像中的应用。方法建立纳米探针,对其表征进行检测。制备乳腺癌小鼠模型,采用纳米探针于小鼠尾静脉注射,采用荧光成像和MRI判断纳米颗粒能否聚集于乳腺癌病灶部位。分别设置对照组、A组(应用四氧化三铁-免疫球蛋白G-吲哚菁绿)、B组(应用曲妥珠单抗+四氧化三铁-曲妥珠单抗-吲哚菁绿)、C组(应用四氧化三铁-曲妥珠单抗-吲哚菁绿)。检测纳米颗粒表征,给予小鼠活体MRI和活体荧光成像检查。结果本实验通过建立SPIONs,纳米颗粒平均粒径为(25.89±3.63)nm。偶联后的纳米颗粒于828处存在明显吸收峰,与荧光染料吲哚菁绿的荧光发射波长相同。纳米颗粒弛豫率较高,达107.67 nM^-1·s^-1。纳米颗粒溶液在近红外激光持续照射后的温度最高达57.85℃。采用纳米探针于小鼠尾静脉注射1 d后,活体MRI癌灶部位T 2信号最低。C组小鼠癌灶部位△T 2值为(30.68±5.14)ms,较对照组(3.13±0.98)ms、A组(4.52±1.15)ms、B组(12.14±2.25)ms显著升高(P<0.05);B组小鼠癌灶部位△T2值较对照组和A组显著升高(P<0.05)。活体荧光成像可见纳米颗粒于小鼠癌灶组织和腹腔脏器出现一过性浓聚,且经膀胱进行排泄,1d后于癌灶部位出现明显聚集。结论构建四氧化三铁-曲妥珠单抗-吲哚菁绿的SPIONs纳米探针可能是HER-2阳性乳腺癌MRI和荧光成像的一种潜在显像剂。

Objective To analyze the application of superparamagnetic iron oxide nanoparticles(SPIONs)in magnetic resonance imaging(MRI)and fluorescence imaging of human epidermal growth factor receptor 2(HER-2)positive breast cancer model.Methods Nano-probe was established and its characterization was detected.Breast cancer mouse model was prepared,and the tail vein of mice was injected with nano-probe.Fluorescence imaging and MRI were used to determine whether the nanoparticles could accumulate in the breast cancer lesion.Control group,group A(using triferrotetraoxy-immunoglobulin G-indocyanine green),group B(using trastuzumab+triferrotetraoxy-trastuzumab-indocyanine green),and group C(using triferrotetraox-trastuzumab-indocyanine green)were set respectively.Nanoparticle characterization was examined and live MRI and in vivo fluorescence imaging were performed in mice.Results The average particle size of SPIONs was(25.89±3.63)nm.The fluorescence emission wave length of indocyanine green was the same as that of indocyanine green.The relaxation rate of nanoparticles was higher,reaching 107.67 nM-1·s-1.Nanoparticles solution after the near-infrared laser light has the highest temperature of 57.85℃.After 1 d of intravenous injection of nano-probe into the tail vein of mice,the T 2 signal at the tumor focus of MRI in vivo was the lowest.The T 2 value(30.68±5.14)ms in the C group was significantly higher than that in the control group(3.13±0.98)ms,group A(4.52±1.15)ms,and group B(12.14±2.25)ms(P<0.05).T 2 value in cancer site of group B was significantly higher than that in control group and group A(P<0.05).In vivo fluorescence imaging showed transient concentration of nanoparticles in the tumor tissue and abdominal organs of mice,which were excreted through the bladder,and obvious aggregation in the tumor site 1 day later.Conclusion The SPIONs nano-probe may be a potential imaging agent for MRI and fluorescence imaging of HER-2 positive breast cancer.