Endocytosis, intracellular transport, and exocytosis of lanthanide-doped upconverting nanoparticles in single living cells

Lanthanide-doped upconverting nanoparticles (UCNPs) have recently attracted enormous attention in the field of biological imaging owing to their unique optical properties (near-infrared excitation followed by photoluminescence in the visible spectral range). For biological applications, it is critical to understand the interaction between these nanoparticles and biological systems at the cellular level. In this paper, using epi-fluorescence microscopy with 980-nm excitation, a full intracellular pathway composed of endocytosis, active transport, and exocytosis was clearly visualized for PEG-phospholipid-coated UCNPs in single HeLa cells, which was experimentally feasible mostly thanks to the excellent photostability and low cytotoxicity thereof. Each step in the pathway was characterized and identified by various chemical inhibition studies and spectroscopic measurements.