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叶酸靶向纳米微泡在乳腺微小癌诊断中的价值研究

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

作者信息

Xue Nianyu, Shen Zhenyu, Xu Zhenbin, Zhang Shengmin

机构信息

Department of Ultrasonography, The First Affiliated Hospital of Ningbo University, Ningbo First Hospital, Ningbo, Zhejiang, China.

出版信息

Front Oncol. 2025 Jul 9;15:1512422. doi: 10.3389/fonc.2025.1512422. eCollection 2025.

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 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. , 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.

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df0c/12283716/25e069ca6009/fonc-15-1512422-g001.jpg

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