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

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  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.