The imaging research of a nano-scaled ultrasound contrast agent with dual targets against HER2 positive breast cancer cell / 中华超声影像学杂志

ABSTRACT

Objective:To prepare a dual targeting nanobubble both for HER2 target and cancer cell target, and compare the targeting ability with single targeting nanobubble either with HER2 targeting or cancer cell targeting ability in vitro.Methods:Nanobubbles(NBs) were prepared using the modified thin film hydration method and then connected with IR783 directly (NBs-IR783), HER2 antibody Affibody by avidin-biotin method (NBs-Affibody), or both of them (IR783-NBs-Affibody). The size distribution, stability, and biosafety of these contrast agents were observed. Flow cytometry and immunofluorescence were applied to compare the binding rate of these NBs against HER2 positive breast cancer cell in vitro.Results:The average size of NBs-Affibody, NBs-IR783 and IR783-NBs-Affibody was (538.4±95.8)nm, (551.8±114.8)nm, and (482.7±54.3)nm, respectively. The binding rate for HER2 positive cell was 26.6%, 97.6%, 84.5%, while for HER2 negative cell was 5.4%, 99.9% and 99.3%, respectively. The results of dual-labeled flow cytometry showed that the binding rate of IR783-NBs-Affibody mediated by IR783 to HER2 positive breast cancer cells were 79.5% and Affibody mediated HER2 targeting binding rate were 19.4%. However, NBs-IR783 only showed IR783-mediated tumor targeted binding without HER2 targeting ability with binding rate of 2.3%.Conclusions:The prepared IR783-NBs-Affibody has the dual targeting ability for HER2 positive breast cancer cell, which is superior to the single targeting NBs (NBs-Affibody and NBs-IR783). IR783-NBs-Affibody is optimal to meet the imaging requirements of tumor heterogeneity.