Engineering Magnetofluorescent Nanoparticles for Neurological Disease Diagnosis Engineered functional nanoparticles can stimulate, respond to, and interact with target proteins, cells or tissues in controlled ways. In this work, we will devise core-shell structured dual-imaging magnetofluorescent nanoparticles (MFNPs) integrating both iron oxide and an inorganic fluorophore, modify their surface to achieve biofunctionality while minimize toxicity to cells or tissues, and apply them in a brain tumor model. The core-shell structure ensures a small diameter for nanoparticles thus increasing bioavailability, and the inorganic fluorophore has a high quantum yield and an excellent stability against photobleaching to ensure higher signal to noise amidst the tissue autofluoroescence background. We will test the hypothesis that the core-shell structured MFNPs can be surface-modified to specifically target glioma brain tumors and imaged with both MR and optical fluorescence imaging. First, MFNPs with core-shell structures will be chemically synthesized from ferrous salts and inorganic near infrared fluorescence dyes, and these nanoparticles will be tuned to the appropriate size, magnetic moment and fluorescence brightness to achieve maximum sensitivity using MRl and fluorescence imaging. Second, to investigate the diagnostic applications ofthe core-shell MFNPs in neuroscience, the MFNPs will be surface-modified by polymer encapsulation to achieve bioconjugation with disease recognition probes, permeation through the BBB, high specific binding to targeting cells or tissues, and colloidal stability in serum (as well as aqueous solutions for long-term storage). Third, MFNPs conjugated with affinity peptide chlorotoxin specific to brain tumor will be injected into rats to permeate through the BBB for the diagnosis of brain tumor by both MR imaging and fluorescence imaging. Integrity ofthe BBB after MFNP crossing and the biodistribution of MFNPs will be investigated using staining and histology.

Public Health Relevance

If the MFNP conjugates are verified to be able to permeate through the BBB for the brain tumor detection, it is believed that the MFNP-based platform technology can be applied to the study of many brain diseases, and provide enabling in vivo tools for early detection and treatment assessment of brain diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103650-03
Application #
8681484
Study Section
Special Emphasis Panel (ZRR1-RI-4)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$222,928
Indirect Cost
$62,874
Name
University of Nevada Reno
Department
Type
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
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