Study on the diagnostic value of folic acid-targeted nano-microbubbles in breast microcarcinoma

Abstract

Abstract Background The prognosis of breast cancer is significantly correlated with its early detection. It is difficult to detect breast microcarcinomas less than or equal to 5 mm by imaging examination. Methods Folic acid-targeted nanobubbles (FA-TNBs) were prepared by the thin-film hydration method. Cytotoxicity and cellular uptake assays were used to examine FA-TNBs’ biological toxicity to cells, targeting them to breast cancer cells. In addition, by constructing a mouse 4T1 tumor model and evaluating the targeting and imaging effects of FA-TNBs, the diagnostic value of these microbubbles for breast microcarcinomas (diameter ≤ 5 mm) was evaluated. Results The average particle size of the fabricated FA-TNBs was 244 ± 21 nm. In vitro cell uptake experiments showed that breast cancer 4T1 cells take up more FA-TNBs than non-targeted nanobubbles (N-TNBs) (p < 0.001). In the cytotoxicity experiment, the survival rate of 4T1 cells under each FA-NBs concentration was > 90%. In vivo imaging of the mouse 4T1 tumor model showed that compared with the N-TNBs group, the FA-TNBs group took a shorter time to peak (20 s, 40 s, p < 0.05), had a higher peak intensity (38.3 ± 1.5 dB, 31.7 ± 1.5 dB, p < 0.05), and the extinction time was shorter (180 s, 120 s, p < 0.05). After FA-NB injection, there were no apparent abnormalities in the tissue sections or hematological examinations of the mice’s vital organs. Conclusions The prepared FA-TNBs had good water solubility, safety, biocompatibility, and enhancement of ultrasound imaging. It had a good imaging effect on mouse breast cancer tumors with a diameter of 5 mm and showed apparent active targeting. FA-TNBs may become a new and practical ultrasound contrast agent for the early detection of breast cancer.