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Recently, the investigation of the interactions between nanomaterials and biological systems (known as nano-bio interactions)
has spurred tremendous research interest in the field of nanotechnology. To improve the therapeutic potential of the
nanoparticle (NP)-based vehicles for the intracellular delivery, it is crucial to systematically study the fate of NPs with uniformity
of particle size, shape and surface charge, which are desired for elucidating the effects of these properties on cell uptake and biodistribution.
Anthanide-doped upconversion nanoparticles (UCNPs) provide a novel BBB delivery approach, as their shape/
size/surfaces are tunable. Furthermore, these nanoparticles have excellent detection characteristics such as background free,
photo stable, and deep tissue penetration. In this work, we compared a series of upconversion nanoparticles (UCNPs), including
original UCNPs, OA-free UCNPs, DNA-modified UCNPs, SiO2-coated UCNPs and PEG-conjugated UCNPs to analyze the
principle factors that facilitate the transport of nanoparticles into the mouse NSC-34 motor neuron cells. It is found that
UCNPs cellular uptake is mainly dependent on the dispersity in cell culture media. The surface charge plays an important role
during this procedure as well. Specifically, PEG-conjugated UCNPs showed the most excellent cell uptake ability among these
five types of UCNPs. While, the original UCNPs were primarily found attached on the cell membrane, because they formed
aggregation in the cell culture media. The cytotoxicity of the UCNPs in NSC-34 cells demonstrated that the PEG-conjugated
UCNPs possessed minimal cellular viability. Through this work, the results highlight the potential application of constructing
a multifunctional UCNPs nano-composite with integration of brain drug delivery, diverse biomolecule monitoring and deep
tissue imaging.