Screen-Based Analysis of Magnetic Nanoparticle Libraries Formed Using Peptidic Iron Oxide Ligands

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• 作者：Mariya Barch ; Satoshi Okada ; Benjamin B. Bartelle ; Alan Jasanoff
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：September 10, 2014
• 年：2014
• 卷：136
• 期：36
• 页码：12516-12519
• 全文大小：258K
• ISSN：1520-5126

文摘

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鈥揑ONP 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鈥揑ONP complex displayed stability in biological buffer and induced persistent MRI contrast in mice, indicating suitability of these species for in vivo molecular imaging applications.