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Biomedical Imaging with NIR Upconverting Nanoparticles

Cross-sectional slice of NaGdF4: Yb/Er NPs in fibroblast cells.

Rare-earth doped nanoparticles (NPs) are known to have exceptional optical properties such as strong absorption and sharp emission lines. Since the optical properties are due to the f-f electron transitions, these nanoparticles do not photobleach like organic dyes or blink like quantum dots. Through the process known as upconversion, rare-earth ions can convert multiple lower energy photons into higher energy ones. We utilize this to engineer our NPs to absorb near-infrared light (980 nm) and emit in the visible (550 nm, 660 nm) and NIR (800 nm). Also, these NPs do not require high energy densities such as conventional two-photon processes and can be excited with pulsed and continuous sources, making them ideal for biomedical purposes. The 980 nm excitation for ytterbium and erbium co-doped systems, such as the KMgF3: Yb/Er and NaGdF4: Yb/Er NPs used herein, is advantageous due to the low scattering and absorption of tissue in this region.

Fibroblast cells were grown in multiwell plates and incubated with 100μg/mL doses of NPs. In order to image the cells with PEGylated nanoparticles, DAPI was used to stain the nucleus (blue), and a phalloidin stain for the cytoplasm  (red). The cells were then  treated with upconverting nanoparticles, and 3D images were obtained with a multiphoton microscope. It was seen that the PEGylated NPs are easily taken up by the cells and migrate into the nucleus. The light blue and green are correlated to upconversion emission which came from inside the nucleus and cytoplasm, respectively, showing that at the time of fixing, some NPs were in the process of migrating into the nucleus. These NPs will be very useful for cancer labeling , theranostics, and selective killing of cells through infrared photodynamic therapy.