Molecular UpconversionNanoparticles for Live-CellImaging

Precise molecular control has become a highly attractive feature to develop the next generation of upconversion materials for autofluorescence-free deep tissue imaging. However, in aqueous environments, upconversion molecules are orders of magnitude dimmer than inorganic upconversion nanoparticles, thereby strongly limiting their applicability to bioimaging. By encapsulating ca. 1,900 upconversion molecules into sub-40 nm polymer nanoparticles, we show that molecular precision and nanomaterial brightness can be combined into a new type of hybrid nanomaterial. The brightness of these molecular upconversion nanoparticles (UCMol-NPs) is almost on par with widely used inorganic upconversion nanoparticles, permitting the experimental demonstration of live-cell imaging with UCMol-NPs, an important step toward advancing molecular upconversion into the application era. Fabrication, characterization, and modeling of UCMol-NPs with various sizes and loadings reveal that significant brightness enhancement is possible. This will be paramount for advancing upconversion beyond the current limits of inorganic nanoparticles and translating them into clinical applications.