Near-infrared mediated orthogonal bioimaging and intracellular tracking of upconversion nanophotosensitizers.

Although upconversion photodynamic therapy (PDT) has gained extensive interests in disease treatment, the intracellular migration pathway of upconversion photosensitizers and underlying cell-particle interaction mechanism is still largely unexplored. In this work photoswitchable upconversion nanoparticles (UCNPs) are reported  that can release orthogonal emissions excited by two near-infrared lights, i.e., red color of 980-nm and green color of 808-nm light excitation. Taking advantage of the dual-emissive property, a methodology based on Pearson's correlation analysis is proposed to verify the accuracy of upconversion luminescence signals under different excitation lights, which has been previously neglected. Meanwhile, we have designed a near-infrared mediated bioimaging nanoplatform that can generate reactive oxygen species (ROS) using one light and simultaneously track the location of upconversion photosensitizers using another excitation light. Our study not only depicts the migration pathway of upconversion photosensitizers, but also demonstrates the organelle escape of these upconversion nanoparticles via PCI (photochemical internalization) process. It is believed that our results inspire more efficient synergistic therapy by combining PDT with other modalities in a programmable manner.