Up-Converting Phosphor Nanoparticles Coated with Long a Wavelength Fluorophore to Enable 978 nm Excitation and 780 nm Emission for Deep Tissue Imaging for Theranostics

Deep tissue imaging requires the combination of long wavelength excitation and emission to avoid absorption by tissue in vivo. Theranostics, which combines imaging and therapeutic drug delivery, will also be aided by being able to image deeply in vivo. We present a new nanoparticle construct that enables long-wavelength imaging, and encapsulation of therapeutics. It is based on the ability of Flash NanoPrecipitation (FNP) to assemble hydrophobic inorganic and organic species in a single precipitation step. The NPs are based on 72 nm diameter upconverting phosphors (UCPs) that are excited at 980 nm and emit at shorter wavelengths. The UCPs are coated in the precipitation step with a layer of fluorescent dye, DiR, that is excited at the emission wavelength of the UCP. However, the shorter wavelength excitation of the UCP is transferred by Förster energy transfer rather than radiative excitation. The DiR on the UCP surface strongly emits with a maximum at 780 nm. These upconverting nanoparticles (UCNPs) have three distinctive advantages: The UCPs excitation, at 978 nm, is driven by high power, inexpensive laser diodes used for fiber optic communications. Second, the large wavelength difference between excitation (980 nm) and emission (780 nm) reduces the problem of blocking filters that are required when the adsorption and emission spectra closely overlap. Third, both excitation and emission wavelength are in the “imaging window” with minimal absorption from tissue, blood, or water. These advantages make this an attractive platform for developing theranostic NPs. The incorporation of therapeutic compounds into this upconverting nanoparticle (UCNP) platform is presented.