肿瘤靶向双模态MR/NIRF成像探针早期检测三阴性乳腺癌脑转移

IF 6.6 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI:10.2147/IJN.S498629

Fang Nie, Lin Li, Yingying Bai, Jian Yang

{"title":"肿瘤靶向双模态MR/NIRF成像探针早期检测三阴性乳腺癌脑转移","authors":"Fang Nie, Lin Li, Yingying Bai, Jian Yang","doi":"10.2147/IJN.S498629","DOIUrl":null,"url":null,"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.","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3697-3712"},"PeriodicalIF":6.6000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932937/pdf/","citationCount":"0","resultStr":"{\"title\":\"Early Detection of Brain Metastases from Triple-Negative Breast Cancer with a Tumor-Targeting Dual-Modal MR/NIRF Imaging Probe.\",\"authors\":\"Fang Nie, Lin Li, Yingying Bai, Jian Yang\",\"doi\":\"10.2147/IJN.S498629\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":14084,\"journal\":{\"name\":\"International Journal of Nanomedicine\",\"volume\":\"20 \",\"pages\":\"3697-3712\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932937/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Nanomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJN.S498629\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"NANOSCIENCE & NANOTECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S498629","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

目的：由于血脑屏障（BBB）的存在，早期三阴性乳腺癌（TNBC）脑转移的影像学具有挑战性。为了解决这个问题，我们开发了Den-Angio-GE11，一种纳米探针，可以穿过血脑屏障，选择性地靶向转移细胞。方法：通过心内注射MDA-MB-231寻脑细胞（MDA-MB-231- br）建立小鼠TNBC脑转移模型。采用t2加权磁共振成像（MRI）纵向监测转移病灶，并通过钆- dtpa （Gd-DTPA）增强MRI确诊。在PAMAM -G5树状大分子平台上合成了deno - angioo -GE11纳米探针，结合Angiopep-2和GE11肽，用于血脑屏障穿越和转移细胞靶向。通过偶联Gd-DTPA用于MRI和NIR783用于近红外荧光（NIRF）成像，实现了双峰成像能力。结果：免疫荧光染色和流式细胞术检测证实，与对照组相比，Den-Angio-GE11对EGFR的亲和力显著增强。注射MDA-MB-231BR细胞三周后，在t2加权MRI上出现脑转移，并在另外一到两周内保持血脑屏障功能未受损，gd - dtpa增强MRI显示缺乏增强。与对照纳米颗粒相比，给药后Den-Angio-GE11显著增强病变T1和NIRF信号。组织学分析证实Den-Angio-GE11靶向脑转移细胞。对于极早期病变（t2加权成像无法检测到），den - angio - ge11给药后的NIRF成像成功地显示了潜在的病变。荧光成像分析进一步证实了Den-Angio-GE11靶向脑实质中零星转移细胞。结论：通过t1加权MRI或NIRF成像，Den-Angio-GE11可检测TNBC早期脑转移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

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

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.