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Guo, Peng; Huang, Jing; Wang, Liya; Di Jia; Yang, Jiang; Dillon, Deborah A.; Zurakowski, David; Mao, Hui; Moses, Marsha A.; Auguste, Debra T.
Proceedings of the National Academy of Sciences - PNAS, 10/2014, Letnik: 111, Številka: 41Journal Article
Significance Triple negative breast cancers (TNBCs) have a poor prognosis (5-y survival of 74.5%) among all breast cancer patients (5-y survival of greater than 95%) because of the aggressiveness of the disease and the lack of targeted therapeutics. We show that intercellular adhesion molecule-1 (ICAM-1) is differentially expressed in human TNBC tumor tissues by immunohistochemistry and in human TNBC cell lines via quantification of gene and protein expression. Iron oxide nanoparticles functionalized with ICAM-1 antibody (ICAM-IONP) were synthesized as MRI probes. An in vivo signal enhancement of 2.6-fold for ICAM-IONPs was measured relative to controls, demonstrating that ICAM-1 is a potential diagnostic and therapeutic target for TNBC treatment. Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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