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Casein-Coated Iron Oxide Nanoparticles for High MRI Contrast Enhancement and Efficient Cell Targeting
journal contribution
posted on 2013-06-12, 00:00 authored by Jing Huang, Liya Wang, Run Lin, Andrew Y. Wang, Lily Yang, Min Kuang, Weiping Qian, Hui MaoSurface properties, as well as inherent
physicochemical properties,
of the engineered nanomaterials play important roles in their interactions
with the biological systems, which eventually affect their efficiency
in diagnostic and therapeutic applications. Here we report a new class
of MRI contrast agent based on milk casein protein-coated iron oxide
nanoparticles (CNIOs) with a core size of 15 nm and hydrodynamic diameter
∼30 nm. These CNIOs exhibited excellent water-solubility, colloidal
stability, and biocompatibility. Importantly, CNIOs exhibited prominent T2 enhancing capability with a transverse relaxivity r2 of 273 mM–1 s–1 at 3 tesla. The transverse relaxivity is ∼2.5-fold higher
than that of iron oxide nanoparticles with the same core but an amphiphilic
polymer coating. CNIOs showed pH-responsive properties, formed loose
and soluble aggregates near the pI (pH ∼4.0). The aggregates
could be dissociated reversibly when the solution pH was adjusted
away from the pI. The transverse relaxation property and MRI contrast
enhancing effect of CNIOs remained unchanged in the pH range of 2.0–8.0.
Further functionalization of CNIOs can be achieved via surface modification
of the protein coating. Bioaffinitive ligands, such as a single chain
fragment from the antibody of epidermal growth factor receptor (ScFvEGFR),
could be readily conjugated onto the protein coating, enabling specific
targeting to MDA-MB-231 breast cancer cells overexpressing EGFR. T2-weighted MRI of mice intravenously administered
with CNIOs demonstrated strong contrast enhancement in the liver and
spleen. These favorable properties suggest CNIOs as a class of biomarker
targeted magnetic nanoparticles for MRI contrast enhancement and related
biomedical applications.