Plasmon Resonance Energy Transfer (PRET)-based Molecular Imaging of Cytochrome<i>c</i>in Living Cells

We describe the development of innovative plasmon resonance energy transfer (PRET)-based molecular imaging of biomolecules in living cells. Our strategy of in vivo PRET imaging relies on the resonant plasmonic energy transfer from a gold nanoplasmonic probe to conjugated target molecules, which creates “quantized quenching dips” within the Rayleigh scattering spectrum of the probe. The positions of these quantized quenching dips exactly match with the absorption peaks of the target molecule since we intentionally design nanoantennas (i.e., nanoplasmonic probes) to overlap the electronic dipoles of the molecule and the plasmonic resonance dipole of nanoantennas. Such the quenching dips allow quantitative and long-term dynamic imaging of the target molecule without the drawbacks of photobleaching and blinking inherent to fluorescent markers, which cannot provide chemical fingerprints. Compared with other imaging methods, our PRET spectroscopic imaging method allows us to generate nanoscale specific wavelengths of local light sources in living systems via nanoantennas and transmit back the nanospectroscopic imaging data of biochemical activities in living cells. As a first demonstration of in vivo PRET imaging, we performed a visualization of the dynamics of intracellular cytochrome c in HepG2 cells under ethanol-induced apoptosis.