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Title: Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors

Journal Article · · Breast Cancer Research
DOI:https://doi.org/10.1186/bcr3050· OSTI ID:1626697
 [1];  [2];  [3];  [2];  [4];  [5];  [6];  [7];  [5];  [5];  [8];  [9];  [10]
  1. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Cell Biology and Physiology; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center
  2. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology
  3. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Biochemistry and Molecular Biology
  4. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Cell Biology and Physiology
  5. Senior Scientific LLC, Albuquerque, NM (United States)
  6. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nanomaterials Sciences Dept.
  7. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology; Senior Scientific LLC, Albuquerque, NM (United States)
  8. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies
  9. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology
  10. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Senior Scientific LLC, Albuquerque, NM (United States)
+ Show Author Affiliations

Introduction: Breast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry. Methods: To accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry. Results: We demonstrated a time- and antigen concentration-dependent increase in the number of antibodyconjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2- expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system. Conclusions: These results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection.

Research Organization:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC04-94AL85000
OSTI ID:
1626697
Journal Information:
Breast Cancer Research, Vol. 13, Issue 5; ISSN 1465-542X
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (17)

Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging: MRI applications of high relaxivity contrast agents journal May 2016
Cancer active targeting by nanoparticles: a comprehensive review of literature journal July 2014
Functionalization of iron oxide nanoparticles with clove extract to induce apoptosis in MCF-7 breast cancer cells journal February 2020
Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer journal October 2018
How can nanotechnology help the fight against breast cancer? journal January 2018
Estimation of magnetic moment and anisotropy energy of magnetic markers for biosensing application journal May 2016
Temperature trends and correlation between SQUID superparamagnetic relaxometry and dc-magnetization on model iron-oxide nanoparticles journal January 2020
Magnetic responsive cell-based strategies for diagnostics and therapeutics journal August 2018
Modulation of cytotoxic and genotoxic effects of nanoparticles in cancer cells by external magnetic field journal June 2014
Membrane expression of thymidine kinase 1 and potential clinical relevance in lung, breast, and colorectal malignancies journal September 2018
Functionalized rare earth-doped nanoparticles for breast cancer nanodiagnostic using fluorescence and CT imaging journal March 2018
Magnetic iron oxide nanoparticles as drug carriers: preparation, conjugation and delivery journal April 2018
Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-l-lysine-Assisted Magnetic Iron Oxide Nanoparticles journal July 2015
Revealing Glycoproteins in the Secretome of MCF-7 Human Breast Cancer Cells journal January 2015
Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin journal July 2013
Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells journal January 2016
Incorporating gold nanoclusters and target-directed liposomes as a synergistic amplified colorimetric sensor for HER2-positive breast cancer cell detection journal January 2017

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