TY - JOUR
T1 - Screen-based analysis of magnetic nanoparticle libraries formed using peptidic iron oxide ligands
AU - Barch, Mariya
AU - Okada, Satoshi
AU - Bartelle, Benjamin B.
AU - Jasanoff, Alan
N1 - Publisher Copyright:
© 2014 American Chemical Society.
PY - 2014/9/10
Y1 - 2014/9/10
N2 - The identification of effective polypeptide ligands for magnetic iron oxide nanoparticles (IONPs) could considerably accelerate the high-throughput analysis of IONP-based reagents for imaging and cell labeling. We developed a procedure for screening IONP ligands and applied it to compare candidate peptides that incorporated carboxylic acid side chains, catechols, and sequences derived from phage display selection. We found that only l-3,4-dihydroxyphenylalanine (DOPA)-containing peptides were sufficient to maintain particles in solution. We used a DOPA-containing sequence motif as the starting point for generation of a further library of over 30 peptides, each of which was complexed with IONPs and evaluated for colloidal stability and magnetic resonance imaging (MRI) contrast properties. Optimal properties were conferred by sequences within a narrow range of biophysical parameters, suggesting that these sequences could serve as generalizable anchors for formation of polypeptide-IONP complexes. Differences in the amino acid sequence affected T1- and T2-weighted MRI contrast without substantially altering particle size, indicating that the microstructure of peptide-based IONP coatings exerts a substantial influence and could be manipulated to tune properties of targeted or responsive contrast agents. A representative peptide-IONP complex displayed stability in biological buffer and induced persistent MRI contrast in mice, indicating suitability of these species for in vivo molecular imaging applications.
AB - The identification of effective polypeptide ligands for magnetic iron oxide nanoparticles (IONPs) could considerably accelerate the high-throughput analysis of IONP-based reagents for imaging and cell labeling. We developed a procedure for screening IONP ligands and applied it to compare candidate peptides that incorporated carboxylic acid side chains, catechols, and sequences derived from phage display selection. We found that only l-3,4-dihydroxyphenylalanine (DOPA)-containing peptides were sufficient to maintain particles in solution. We used a DOPA-containing sequence motif as the starting point for generation of a further library of over 30 peptides, each of which was complexed with IONPs and evaluated for colloidal stability and magnetic resonance imaging (MRI) contrast properties. Optimal properties were conferred by sequences within a narrow range of biophysical parameters, suggesting that these sequences could serve as generalizable anchors for formation of polypeptide-IONP complexes. Differences in the amino acid sequence affected T1- and T2-weighted MRI contrast without substantially altering particle size, indicating that the microstructure of peptide-based IONP coatings exerts a substantial influence and could be manipulated to tune properties of targeted or responsive contrast agents. A representative peptide-IONP complex displayed stability in biological buffer and induced persistent MRI contrast in mice, indicating suitability of these species for in vivo molecular imaging applications.
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U2 - 10.1021/ja410884e
DO - 10.1021/ja410884e
M3 - Article
C2 - 25158100
AN - SCOPUS:84907486674
SN - 0002-7863
VL - 136
SP - 12516
EP - 12519
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 36
ER -