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Diagnostic Applications

Magnetic Nanoparticles

Magnetic nanoparticles (MNPs) have been explored as therapeutic and/or diagnostic tool in medicine. In diagnosis MNPs can serve as contrast agents in magnetic resonance imaging (MRI) [126], cell separation [127,128], purification [129,130], and gene transfer [131,132]. MNPs can be applied as a delivery system for targeted therapy [132] and hyperthermia treatment [133,134]. Detection and immobilization of biomolecules can also be performed by MNPs [135—137]. Numerous diseases may be diagnosed with MNPs such Alzheimer disease [138], gliomas [139], cardiovascular diseases [140], cancer [141,142], and central nervous system autoimmune diseases [143].

Table 7.2 Peptide and protein drugs currently in clinical trials

Molecule

Protein/peptide

Company

Stage/

phase

Disease

Epoetin alpha

Protein erythropoietin

University Iowa

II

Neonatal anemia

Daclizumab

Monoclonal antibody

Biogen

III

Relapsing-remitting multiple sclerosis

Human recombinant CC10

Recombinant human protein

Clarassance, Inc.

I

Respiratory distress syndrome in infant

RBX2660

Protein

Rebiotix Inc.

II

Clostridium difficile infection

Sikirumab

Human anti-interleukin-6 monoclonal antibody

GlaxoSmithKline

III

Giant cell arteritis

ABT-494

Protein

Abbvie

III

Rheumatoid arthritis

FP-1039

Five Prime Therapeutics, Inc.

TaiMed Biologics Inc.

I

Cancer

Ibalizumab

Monoclonal antibody

III

Human immunodeficiency virus

GW572016

Tyrosine kinase inhibitor

University of New Mexico

I/II

Breast cancer

TTI-621

Fusion protein

Trillium Therapeutics

1

Hematologic malignancies

Ixekizumab/LY2439821

Monoclonal antibody

Eli Lilly

III

Psoriatic arthritis

Nilotinib/AMN107

Kinase inhibitor

Novartis Pharmaceuticals

I/II

Leukemia

https://clinicaltrials.gov/.

MNP has been developed and designed to detect targets such as proteins, peptides, DNA, RNA, pathogens, and tumors. In cardiac diseases, MNP has been utilized to detect plaque. Profilin-1 targeted MNPs were applied to investigate atherosclerosis characteristics in mice model [144]. MNP conjugated with polyclonal profilin-1 antibody and fluorescence dye (PC-NPs) was intravenously administered to atherosclerosis mice model [144]. Immunofluorescence assay discovered high levels of profilin-1 protein inside plaque of diseased mice. Imaging studies showed accumulation of PC-NP in atherosclerotic plaque of carotid artery [144]. This dual-imaging probe may also be applied in diagnosis ofplaque in cardiac patients. Another dual molecular probe was explored in ovarian cancer cells. The transfection efficiency of SPION and short hairpin RNA dual-function molecular probe was explored at different iron concentrations (5, 15, 30, 45, 75, and 100mg/L) [145]. Cell survival rate was above 90% for the first three concentrations and was below 75% for the last three concentrations [145]. When the concentration of the probe was greater than or equal to 45 mg/L, the inhibition of the protein expression level of epidermal growth factor receptor was elevated [145]. MRI analysis displayed lower signal strength with increase in iron concentration in the probe with SKOV3 cell line [145]. These results provide an insight on the role of iron in SPION for diagnosis and treatment. A DNA point mutation can be detected by single based coded (CdS) MNP probes [146]. Adenosine, cytidine, guanosine, and thymidine (A-CdS, C-CdS, G-CdS, and T-CdS) base probes were applied in identifying mutations in DNA [146]. Resonance frequency analysis revealed a change on DNA strand when a mutation was identified. These results were also confirmed with fluorescence analysis [146]. It appears that this technology can be valuable to detect point mutation in DNA strand and can be developed to diagnose genetic cause of diseases.

 
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