SHG nanoprobes inside a living zebrafish.
SHG nanoprobes inside a living zebrafish

Given that in many experimental settings fluorescent probes fall short of their potential due to bleaching, signal saturation, and tissue autofluorescence, we introduced Second Harmonic Generating (SHG) nanoprobes as superior imaging labels suitable for in vivo imaging, circumventing many of the inherent drawbacks encountered with fluorescent probes.

Since their nanocrystalline structure lacks a central point of symmetry, they are capable of generating SHG signal under intense illumination - converting two photons into one photon of half the incident wavelength – and can be detected by conventional two-photon microscopy.

Since the optical signal of SHG nanoprobes is based on scattering, rather than absorption as in the case of fluorescent probes, they neither bleach nor blink, and the signal does not saturate with increasing illumination intensity. When SHG nanoprobes are used to image live tissue, the SHG signal can be detected with little background signal, and they are physiologically inert, showing long-term photostability. Hence, SHG nanoprobes provide unique advantages for molecular in vivo imaging with unmatched sensitivity and temporal resolution.

Ideally, contrast agents for biomedical applications should degrade in vivo without any long term toxicological consequences to the organism. To address this need, we are currently developing biodegradable SHG (bioSHG) nanoprobes to enable an innovative approach to cancer treatment using targeted high-resolution optical imaging for diagnostics and therapy.