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Project 5

$263,415P20FY2012GMNIH

University Of Nevada Reno, Reno NV

Investigators

Linked publications & trials

Abstract

Enigneering Magnetofluorescent Nanoparticles for Neurological Disease Diagnosis Engineered funcfional nanoparticles can sfimulate, respond to, and interact with target proteins, cells or fissues in controlled ways. In this work, we will devise core-shell structured dual-imaging magnetofluorescent nanoparticles (MFNPs) integrafing both iron oxide and an inorganic fluorophore, modify their surface to achieve biofuncfionality 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 fissue autofiuoroescence 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 opfical fluorescence imaging. First, MFNPs with core-shell structures will be chemically synthesized from ferrous salts and inorganic nearinfrared 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 diagnosfic applicafions ofthe core-shell MFNPs in neuroscience, the MFNPs will be surface-modified by polymer encapsulation to achieve bioconjugation with disease recognition probes, permeafion through the BBB, high specific binding to targefing cells or fissues, and colloidal stability in serum (as well as aqueous solufions for long-term storage). Third, MFNPs conjugated with affinity pepfide 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 biodistribufion of MFNPs will be investigated using staining and histology.

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