Work

Early Detection of Brain Metastases from Triple-Negative Breast Cancer with a Tumor-Targeting Dual-Modal MR/NIRF Imaging Probe

Year: 2025

Type: article

Abstract: Objective: Imaging early-stage brain metastases from triple-negative breast cancer (TNBC) is challenging due to the blood-brain barrier (BBB). To address this issue, we developed Den-Angio-GE11, a nanoprobe engineered to traverse the BBB and selectively target metastatic cells. Methods: A TNBC brain metastasis model was established in mice through intracardiac injection of MDA-MB-231 brain-seeking cells (MDA-MB-231-BR). Metastatic lesions were longitudinally monitored using T2-weighted magnetic resonance imaging (MRI) and confirmed through contrast-enhanced MRI with Gadolinium-DTPA (Gd-DTPA). The Den-Angio-GE11 nanoprobe was synthesized on a polyamidoamine (PAMAM)-G5 dendrimer platform, incorporating Angiopep-2 and GE11 peptides for BBB traversal and metastatic cell targeting. Dual-modal imaging capability was achieved by conjugating Gd-DTPA for MRI and NIR783 for near-infrared fluorescence (NIRF) imaging. Results: Den-Angio-GE11 demonstrated significantly enhanced affinity to EGFR compared to controls, as confirmed by immunofluorescence staining and flow cytometry assays. Brain metastases appeared on T2-weighted MRI three weeks post-injection of MDA-MB-231BR cells and maintained uncompromised BBB function for another one or two weeks, as demonstrated by a lack of enhancement in Gd-DTPA-enhanced MRI. Compared to control nanoparticles, Den-Angio-GE11 remarkably enhanced T1 and NIRF signals of lesions after administration. Histological analysis confirmed Den-Angio-GE11 targeting brain metastatic cells. For lesions in extreme-early stage (undetectable by T2-weighted imaging), NIRF imaging post-Den-Angio-GE11 administration successfully indicated potential lesions. Fluorescence imaging analyses further verified Den-Angio-GE11 targeted sporadically metastatic cells in the brain parenchyma. Conclusion: Early brain metastases of TNBC can be detected by Den-Angio-GE11 through T1-weighted MRI or NIRF imaging.

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s498629

Authors: Fang Nie, Lin Li, Yingying Bai, Jian Yang

Institutions: Zhongda Hospital Southeast University, Southeast University, Jiangsu Provincial Hospital of Traditional Chinese Medicine, State Key Laboratory of Digital Medical Engineering

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836