[Preclinical application of MR and fluorescent dual-modality imaging combined with photothermal therapy in HER-2 positive breast cancer].

Objective: 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 in vitro and in vivo . Methods: 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. Results: 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 ( P <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. Conclusion: 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.