ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1512422
Study on the Diagnostic Value of Folic Acid-Targeted Nano-Microbubbles in Breast Microcarcinoma
Provisionally accepted- Department of Ultrasonography, First Affiliated Hospital of Ningbo University, Ningbo, China
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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 4T1 tumor mouse models and evaluating the targeting and imaging effects of FA-TNBs.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-TNBs concentration was over 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-TNB 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 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.
Keywords: Folic Acid, breast cancer, Microbubble, Ultrasonography, diagnosis
Received: 16 Oct 2024; Accepted: 23 Jun 2025.
Copyright: © 2025 Xue, Shen, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Nianyu Xue, Department of Ultrasonography, First Affiliated Hospital of Ningbo University, Ningbo, China
Shengmin Zhang, Department of Ultrasonography, First Affiliated Hospital of Ningbo University, Ningbo, China
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