We have created unique near-infrared (NIR)-emitting nanoscale metal-organic frameworks (nano-MOFs) incorporating a high density of Yb 3+ lanthanide cations and sensitizers derived from phenylene. We establish here that these nano-MOFs can be incorporated into living cells for NIR imaging. Specifically, we introduce bulk and nano-Yb-phenylenevinylenedicarboxylate-3 (nano-Yb-PVDC-3), a unique MOF based on a PVDC sensitizer-ligand and Yb 3+ NIRemitting lanthanide cations. This material has been structurally characterized, its stability in various media has been assessed, and its luminescent properties have been studied. We demonstrate that it is stable in certain specific biological media, does not photobleach, and has an IC 50 of 100 μg/mL, which is sufficient to allow live cell imaging. Confocal microscopy and inductively coupled plasma measurements reveal that nano-Yb-PVDC-3 can be internalized by cells with a cytoplasmic localization. Despite its relatively low quantum yield, nano-Yb-PVDC-3 emits a sufficient number of photons per unit volume to serve as a NIR-emitting reporter for imaging living HeLa and NIH 3T3 cells. NIR microscopy allows for highly efficient discrimination between the nano-MOF emission signal and the cellular autofluorescence arising from biological material. This work represents a demonstration of the possibility of using NIR lanthanide emission for biological imaging applications in living cells with single-photon excitation.uminescent reporters emitting in the near-infrared (NIR) region of the electromagnetic spectrum are highly advantageous for biological imaging applications for several reasons. Biological material has low autofluorescence in the NIR window, which allows facile discrimination between the desired signal of the reporter and the background, leading to an enhanced signalto-noise ratio and improved detection sensitivity (1). Additionally, NIR light scatters less than visible light, and therefore results in increased optical imaging resolution (2, 3). Finally, NIR photons interact less with biological material compared with visible photons, thus decreasing the risk of disturbing or damaging the biological systems being observed.NIR reporters, such as cyanine dyes (4, 5) and quantum dots (6), have previously been shown to be useful for biological imaging applications. However, these materials have broad emission bands that limit their ability to be easily discriminated from the background fluorescence. Additionally, cyanine dyes exhibit limited photostability and quantum dots can display blinking emission, making it difficult to conduct repeated or long-term experiments for such purposes as tracking a moiety or monitoring a process.Several lanthanide cations emit in the NIR and have some advantages with respect to organic fluorophores and semiconductor nanocrystals. Lanthanide cations have narrower emission bandwidths than organic fluorophores and semiconductor nanocrystals. Their emission wavelengths are not affected by the environment, allowing them to be used in a broad ra...