Lanthanide doped upconversion nanoparticles (UCNPs) are promising luminescent materials for biomedical applications due to their ability to convert low energy, non-scattering NIR light to higher energy wavelength emissions. Sensing, bioimaging, drug delivery, therapy and photobiomodulation are the expected biomedical fields that will be impacted by the combination of NIR stimulation and upconversion emission. In the case of a typical upconversion from NIR, energy transfer occurs from Yb<sup>3+</sup> sensitizer ions, which can be excited at 980 nm, to the activator lanthanide ions such as Er<sup>3+</sup>, Tm<sup>3+</sup>, Ho<sup>3+</sup>, Eu<sup>3+</sup>. Synthesis and design of the UCNPs and their introduction into the biological system requires stringent procedures due to the complex nature of biological environment at the cellular level. Our goal in this study is to develop small size, biocompatible UCNPs with a facile microwave assisted synthesis method and utilize them for photobiomodulation of neuronal cells. We aim to elucidate the intracellular mechanisms that are impacted by the upconversion photons emitted from designed nanotransducers towards stimulation of cell function. For this purpose, we sensitized blue emitting NaYF<sub>4</sub> UCNPs and in-vitro laser irradiation experiments are conducted with NG108-15 (neuroblastoma-glioma hybrid) cells. Experiments are designed to further investigate the thermal and chemical effects that contribute to the resulted modifications in the cell function.
Inorganic fluorescent nanoprobes have been widely used as passive agents for intracellular imaging for decades. An emerging field of research is the development of these contrast agents and using them actively in a way that they respond to external stimulation by inducing photo-chemical, thermal or mechanical actions that enable control and modulation over cell function. To achieve such control, methods which are remote, non-invasive and with low-thermal means of stimulation is preferable. Among a large variety of candidates, lanthanide doped upconverting nanoparticles (UCNPs) are one of the most interesting class of fluorescent materials. Non-scattering, low energy near infrared (NIR) light can be used for excitation of UCNPs as on-demand light sources resulting in emission peaks throughout the near-UV and visible wavelengths. Towards this goal, we developed nano-size, hydrophilic, non-toxic and biocompatible core-shell nanoparticles with enhanced upconversion intensity for photo-biomodulation studies. Under this approach, un-doped LaF<sub>3</sub> (inert) shell and Yb<sup>3+</sup> doped LaF<sub>3</sub> (active) shell are grown on core LaF<sub>3</sub>:20% Yb, 2% Tm upconverting nanoparticles for enhanced luminescence for the first time with rapid microwave-assisted synthesis method that employs Polyvinylpyrrolidone (PVP) as biocompatible surfactant. The as-synthesized high efficiency UCNPs are analyzed through XRD, TEM, HRTEM, and Photoluminescence spectrum that is acquired under 980 nm laser excitation. Confocal microscopy is used to visualize nanoparticles in cells. The cellular response to NIR irradiation and upconverted light are visualized by luminescence microscopy.