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...

We report herein the synthesis of a luminescent polynuclear dendritic structure (Sm(III)-G3P-2,3Nap) in which eight Sm(III) ions are sensitized by thirty-two 2,3-naphthalimide chromophores. Upon a single excitation wavelength, the dendrimer complex exhibits two types of emission in the visible and in the near-infrared (NIR) ranges. Sm(III)-G3P-2,3Nap was non-cytotoxic after 24 h of incubation and up to 2.5 μM. The ability of the Sm(III)-based probe to be taken up by cells was confirmed by confocal microscopy. Epifluorescence microscopy validated Sm(III)-G3P-2,3Nap as a versatile probe, capable of performing interchangeably in the visible or NIR for live-cell imaging. As both emissions are obtained from a single complex, the cytotoxicity and biodistribution are inherently the same. The possibility for discriminating the sharp Sm(III) signals from autofluorescence in two spectral ranges increases the reliability of analysis and reduces the probability of artifacts and instrumental errors.

Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta-gonad-mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded Matrigel(TM)-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation.