{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T16:24:58Z","timestamp":1773937498653,"version":"3.50.1"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2019 biological toxicity to cells, targeting them to breast cancer cells. In addition, by constructing 4T1 tumor mouse models and evaluating the targeting and imaging effects of FA-TNBs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The average particle size of the fabricated FA-TNBs was 244 \u00b1 21 nm. <jats:italic>In vitro<\/jats:italic>, cell uptake experiments showed that breast cancer 4T1 cells take up more FA-TNBs than non-targeted nanobubbles (N-TNBs) (p &amp;lt; 0.001). In the cytotoxicity experiment, the survival rate of 4T1 cells under each FA-TNBs concentration was over 90%. <jats:italic>In vivo<\/jats:italic>, 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 &amp;lt; 0.05), had a higher peak intensity (38.3 \u00b1 1.5 dB, 31.7 \u00b1 1.5 dB, p &amp;lt; 0.05), and the extinction time was shorter (180 s, 120 s, p &amp;lt; 0.05). After FA-TNB injection, there were no apparent abnormalities in the tissue sections or hematological examinations of the mice\u2019s vital organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The prepared FA-TNBs had good water solubility, safety, biocompatibility, and enhancement of ultrasound imaging. It had an excellent 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1512422","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:47:04Z","timestamp":1752126424000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Study on the diagnostic value of folic acid-targeted nano-microbubbles in breast 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