Luo X J, Li J, Zhou C W
Department of Diagnostics Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2018 Aug 23;40(8):587-593. doi: 10.3760/cma.j.issn.0253-3766.2018.08.005.
To construct superparamagnetic iron oxide nanoparticles (SPIONs) coated on trastuzumab and indocyanine green (ICG) and then investigate whether the coated nanoparticles (NPs) targeted to human epidermal growth factor receptor-2 (HER-2) receptors on breast cancer cells and . The Fe(3)O(4)-trastuzumab-ICG NPs were constructed. And a series of characteristics of the NPs were evaluated. The uptake ability of SK-BR-3, a HER-2 positive breast cancer cell, was observed by transmission electron microscopy. Then the NPs were injected in the tail veins of SK-BR-3 xenograft tumor-bearing mice to observe the aggregation of NPs in the tumor sites by MRI and fluorescent imaging. Furthermore, when the NPs was gathered at the tumor sites, the near infrared thermal imaging system was used to monitor the tumor temperature after the near infrared radiation. The successfully constructed Fe(3)O(4)-trastuzumab-ICG NPs had the size of (25.93±4.25) nm. The absorption peak was 828 nm, which was as same as the emission wavelength of ICG. The NPs had a high relaxation rate of approximately 107.65 mM(-1)·s(-1). The maximum temperature of NPs solution could reach to 57.8℃ after continuous near infrared laser irradiation. The transmission electron microscopy imaging revealed that the NPs could target and enter into the endoplasmic reticulum of SK-BR-3 cells. MRI analysis showed the lowest T(2) relaxation time in the tumor sites 24 h after tail vein injection of the NPs. The △T(2) of the tumor sites in the Fe(3)O(4)-trastuzumab-ICG group (30.7±4.8) ms was higher compared with that of control group (3.1±1.1) ms, Fe(3)O(4)-IgG-ICG group (4.4±0.9) ms and trastuzumab + Fe(3)O(4)-trastuzumab-ICG group (11.3±3.8) ms., respectively, all showing statistically significant differences (<0.05). The fluorescence imaging revealed that the NPs was concentrated transiently in the intraperitoneal organs and tumor sites, then excreted into the bladder. After 24 h, there was an obvious aggregation in the tumor sites. The near infrared thermal imaging experiments showed that the temperature of tumor sites in Fe(3)O(4)-trastuzumab-ICG group could go up to 49.4℃ after continuous near infrared light irradiation. The newly constructed Fe(3)O(4)-trastuzumab-ICG NPs have the potential to act as a multifunctional imaging agent and a powerful tool for photothermal therapy for HER-2 positive breast cancer.
构建包裹曲妥珠单抗和吲哚菁绿（ICG）的超顺磁性氧化铁纳米颗粒（SPIONs），然后研究包裹后的纳米颗粒（NPs）是否靶向乳腺癌细胞上的人表皮生长因子受体2（HER-2）受体。构建了Fe(3)O(4)-曲妥珠单抗-ICG NPs，并评估了该纳米颗粒的一系列特性。通过透射电子显微镜观察HER-2阳性乳腺癌细胞SK-BR-3的摄取能力。然后将纳米颗粒注射到荷SK-BR-3异种移植瘤小鼠的尾静脉中，通过磁共振成像（MRI）和荧光成像观察纳米颗粒在肿瘤部位的聚集情况。此外，当纳米颗粒在肿瘤部位聚集时，使用近红外热成像系统监测近红外辐射后肿瘤的温度。成功构建的Fe(3)O(4)-曲妥珠单抗-ICG NPs尺寸为(25.93±4.25) nm。吸收峰为828 nm，与ICG的发射波长相同。该纳米颗粒具有约107.65 mM(-1)·s(-1)的高弛豫率。连续近红外激光照射后，纳米颗粒溶液的最高温度可达到57.8℃。透射电子显微镜成像显示，纳米颗粒可靶向并进入SK-BR-3细胞的内质网。MRI分析显示，尾静脉注射纳米颗粒24小时后，肿瘤部位的T(2)弛豫时间最短。Fe(3)O(4)-曲妥珠单抗-ICG组肿瘤部位的△T(2)为(30.7±4.8) ms，高于对照组(3.1±1.1) ms、Fe(3)O(4)-IgG-ICG组(4.4±0.9) ms和曲妥珠单抗+Fe(3)O(4)-曲妥珠单抗-ICG组(11.3±3.8) ms，差异均有统计学意义（<0.05）。荧光成像显示，纳米颗粒短暂集中于腹腔器官和肿瘤部位，然后排泄到膀胱。24小时后，肿瘤部位有明显聚集。近红外热成像实验表明，连续近红外光照射后，Fe(3)O(4)-曲妥珠单抗-ICG组肿瘤部位温度可升至49.4℃。新构建的Fe(3)O(4)-曲妥珠单抗-ICG NPs有潜力作为一种多功能成像剂和用于HER-2阳性乳腺癌光热治疗的有力工具。
