title: Peptide Functionalized Gold Nanoparticles as a Stimuli Responsive Contrast Medium in Multiphoton Microscopy.
abstract: There is a need for biochemical contrast mediators with high signal-to-noise ratios enabling noninvasive biomedical sensing, for example, for neural sensing and protein-protein interactions, in addition to cancer diagnostics. The translational challenge is to develop a biocompatible approach ensuring high biochemical contrast while avoiding a raise of the background signal. We here present a concept where gold nanoparticles (AuNPs) can be utilized as a stimuli responsive contrast medium by chemically triggering their ability to exhibit multiphoton-induced luminescence (MIL) when performing multiphoton laser scanning microscopy (MPM). Proof-of-principle is demonstrated using peptide-functionalized AuNPs sensitive to zinc ions (Zn2+). Dispersed particles are invisible in the MPM until addition of millimolar concentrations of Zn2+upon which MIL is enabled through particle aggregation caused by specific peptide interactions and folding. The process can be reversed by removal of the Zn2+using a chelator, thereby resuspending the AuNPs. In addition, the concept was demonstrated by exposing the particles to matrix metalloproteinase-7 (MMP-7) causing peptide digestion resulting in AuNP aggregation, significantly elevating the MIL signal from the background. The approach is based on the principle that aggregation shifts the plasmon resonance, elevating the absorption cross section in the near-infrared wavelength region enabling onset of MIL. This Letter demonstrates how biochemical sensing can be obtained in far-field MPM and should be further exploited as a future tool for noninvasive optical biosensing.
authors.affiliation: Biomedical Photonics Group, Department of Chemistry and Molecular biology, University of Gothenburg , 412 96 Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Borglin
authors.affiliation: Division of Molecular Physics, Department of Physics, Chemistry, and Biology (IFM), Linköping University , 581 83 Linköping, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Selegård
authors.affiliation: Division of Molecular Physics, Department of Physics, Chemistry, and Biology (IFM), Linköping University , 581 83 Linköping, Sweden.
authors.forename: Daniel
authors.identifier: 0000-0002-7001-9415
authors.initials: D
authors.lastname: Aili
authors.affiliation: Biomedical Photonics Group, Department of Chemistry and Molecular biology, University of Gothenburg , 412 96 Gothenburg, Sweden.
authors.forename: Marica B
authors.identifier: 0000-0002-5987-5915
authors.initials: MB
authors.lastname: Ericson
mesh_terms: D000595:Amino Acid Sequence; D002413:Cations, Divalent / Q000032:analysis; D003287:Contrast Media / Q000737:chemistry*; D019281:Dimerization; D006046:Gold / Q000737:chemistry*; D006801:Humans; D049449:Luminescence; D020783:Matrix Metalloproteinase 7 / Q000032:analysis; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018613:Microscopy, Confocal / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D017785:Photons; D015032:Zinc / Q000032:analysis
chemical_list: D002413:Cations, Divalent; D003287:Contrast Media; D010455:Peptides; D006046:Gold; D020783:Matrix Metalloproteinase 7; D015032:Zinc
keywords: Gold nanoparticles; contrast media; multiphoton microscopy; optical sensing; peptide