Xue Nianyu, Shen Zhenyu, Xu Zhenbin, Zhang Shengmin
Department of Ultrasonography, The First Affiliated Hospital of Ningbo University, Ningbo First Hospital, Ningbo, Zhejiang, China.
Front Oncol. 2025 Jul 9;15:1512422. doi: 10.3389/fonc.2025.1512422. eCollection 2025.
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.
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.
The average particle size of the fabricated FA-TNBs was 244 ± 21 nm. , 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%. , 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.
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.
乳腺癌的预后与其早期检测显著相关。通过影像学检查难以检测出直径小于或等于5mm的乳腺微癌。
采用薄膜水化法制备叶酸靶向纳米气泡(FA-TNBs)。通过细胞毒性和细胞摄取试验检测FA-TNBs对细胞的生物毒性,以及其对乳腺癌细胞的靶向作用。此外,构建4T1肿瘤小鼠模型,评估FA-TNBs的靶向和成像效果。
制备的FA-TNBs平均粒径为244±21nm。细胞摄取实验表明,乳腺癌4T1细胞对FA-TNBs的摄取量多于非靶向纳米气泡(N-TNBs)(p<0.001)。细胞毒性实验中,各FA-TNBs浓度下4T1细胞的存活率均超过90%。小鼠4T1肿瘤模型成像显示,与N-TNBs组相比,FA-TNBs组达到峰值的时间更短(20s、40s,p<0.05),峰值强度更高(38.3±1.5dB、31.7±1.5dB,p<0.05),消退时间更短(180s、120s,p<0.05)。注射FA-TNB后,小鼠重要脏器的组织切片和血液学检查均无明显异常。
制备的FA-TNBs具有良好的水溶性、安全性、生物相容性和超声成像增强效果。对直径5mm的小鼠乳腺癌肿瘤具有优异的成像效果,并表现出明显的主动靶向性。FA-TNBs可能成为一种新型实用的乳腺癌早期检测超声造影剂。