Development of a sensitive, stable and EGFR-specific molecular imaging agent for surface enhanced Raman spectroscopy

作者:Lucas Leanne J; Tellez Claudio; Castilho Maiara L; Lee Christopher L D; Hupman Michael A; Vieira Lais S; Ferreira Isabelle; Raniero Leandro; Hewitt Kevin C*
来源:Journal of Raman Spectroscopy, 2015, 46(5): 434-446.
DOI:10.1002/jrs.4678

摘要

We created and studied a novel nanoprobe for spectroscopic molecular imaging of the epidermal growth factor (EGF) receptor, whose over-expression is a hallmark of a wide range of cancers. Silver nanoparticles (AgNPs) of 45nm diameter were synthesized and coupled to EGF by -lipoic acid, a short ligand that exhibits excellent silver binding affinity. Time-of-flight mass spectroscopy demonstrates formation of the protein complex. Enzyme-linked immunosorbent assay verifies the protein complex is 100% active for the EGF receptor, alone and, following conjugation to silver nanoparticles. Compared with its monosulfide analog, 6-mercaptohexanoic acid, -lipoic acid is stabilized by binding to silver with a total energy that is lower by 1.38eV, as found from Density Functional Theory (DFT)/natural bond analysis calculations. A Highest Occupied Molecular Orbital (HOMO)-Lowest Unoccupied Molecular Orbital (LUMO) gap energy of 5.25 (spin-up electrons) and 5.74eV (spin-down electrons) was obtained for the silver--lipoic acid complex. This is the first report of silver nanoparticles being attached to EGF, and the first theoretical and experimental report on the surface enhanced Raman spectroscopy spectral interpretation of -lipoic acid bound to silver. These nanoprobes exhibit surface enhanced Raman spectroscopy, when aggregated in solution, at picomolar concentrations and have the necessary properties - specificity, sensitivity and stability - to serve as molecular imaging agents.

  • 出版日期2015-5