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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 3/2018

01-06-2018 | Research Article

LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer

Authors: Abedelnasser Abulrob, Slavisa Corluka, Barbara Blasiak, B. Gino Fallone, Dragana Ponjevic, John Matyas, Boguslaw Tomanek

Published in: Molecular Imaging and Biology | Issue 3/2018

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Abstract

Purpose

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, or Her2/neu. Both diagnosis and treatment of TNBC remain a clinical challenge. LyP-1 is a cyclic 9 amino acid peptide that can bind to breast cancer cells. The goal of this study was to design and characterize LyP-1 conjugated to fluorescent iron oxide nanoparticles (LyP-1-Fe3O4-Cy5.5) as a contrast agent for improved and specific magnetic resonance imaging (MRI) in a preclinical model of TNBC.

Procedures

The binding of LyP-1-Fe3O4-Cy5.5 to MDA-MB-231 TNBC cells was evaluated and compared to scrambled peptide bio-conjugated to iron oxide nanoparticles (Ctlpep-Fe3O4-Cy5.5) as a negative control. Following the in vitro study, the MDA-MB-231 cells were injected into mammary glands of nude mice. Mice were divided into two groups: control group received Ctlpep- Fe3O4-Cy5.5 and LyP-1 group received LyP-1-Fe3O4-Cy5.5 (tail vein injection at 2 mg/kg of Fe3O4). Mice were imaged with an in vivo fluorescence imager and a 9.4 T MRI system at various time points after contrast agent injection. The T2 relaxation time was measured to observe accumulation of the contrast agent in breast tumor and muscle for both targeted and non-targeted contrast agents.

Results

Immunofluorescence revealed dense binding of the LyP-1-Fe3O4-Cy5.5 contrast agent to MDA-MB-231 cells; while little appreciable binding was observed to the scrambled negative control (Ctlpep-Fe3O4-Cy5.5). Optical imaging performed in tumor-bearing mice showed increased fluorescent signal in mammary gland of animals injected by LyP-1-Fe3O4-Cy5.5 but not Ctlpep- Fe3O4-Cy5.5. The results were confirmed ex vivo by the 2.6-fold increase of fluorescent signal from LyP-1-Fe3O4-Cy5.5 in extracted tumors when compared to the negative control. In MR imaging studies, there was a statistically significant (P < 0.01) difference in normalized T2 between healthy breast and tumor tissue at 1, 2, and 24 h post injection of the LyP-1-Fe3O4-Cy5.5. In animals injected with LyP-1-Fe3O4, distinct ring-like structures were observed with clear contrast between the tumor core and rim.

Conclusion

The results demonstrate that LyP-1-Fe3O4 significantly improves MRI contrast of TNBC, hence has the potential to be exploited for the specific delivery of cancer therapeutics.
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Metadata
Title
LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer
Authors
Abedelnasser Abulrob
Slavisa Corluka
Barbara Blasiak
B. Gino Fallone
Dragana Ponjevic
John Matyas
Boguslaw Tomanek
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 3/2018
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-017-1140-4

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