Reversible Light-Triggered Stretching of Small-Molecule Photochromic Organic Nanoparticles.

Functional organic nanomaterials are nowadays largely spread in the field of nanomedicine. In situ modulation of their morphology is thus expected to considerably impact their interactions with the surroundings. In this context, photoswitchable nanoparticles that are manufactured, amenable to extensive disassembling upon illumination in the visible, and reversible reshaping under UV exposure. Such reversibility turns to be strongly impaired for photochromic nanoparticles in close contact with a substrate. In situ atomic force microscopy investigations at the nanoscale actually reveal progressive disintegration of the organic nanoparticles under successive UV-vis cycles of irradiation, in the absence of intrinsic elastic forces. These results point out the dramatic interactions exerted by surfaces on the cohesion of non-covalently bonded organic nanoparticles. They invite to harness such systems, often used as biomarkers, to also serve as photoactivatable drug delivery nanocarriers.

Specific Targeting of Mesothelin-Expressing Malignant Cells Using Nanobody-Functionalized Magneto-Fluorescent Nanoassemblies.

Introduction: Most current anti-cancer therapies are associated with major side effects due to a lack of tumor specificity. Appropriate vectorization of drugs using engineered nanovectors is known to increase local concentration of therapeutic molecules in tumors while minimizing their side effects. Mesothelin (MSLN) is a well-known tumor associated antigen overexpressed in many malignancies, in particular in malignant pleural mesothelioma (MPM), and various MSLN-targeting anticancer therapies are currently evaluated in preclinical and clinical assays. In this study, we described, for the first time, the functionalization of fluorescent organic nanoassemblies (NA) with a nanobody (Nb) targeting MSLN for the specific targeting of MSLN expressing MPM cancer cells. Methods: Cell lines from different cancer origin expressing or not MSLN were used. An Nb directed against MSLN was coupled to fluorescent NA using click chemistry. A panel of endocytosis inhibitors was used to study targeted NA internalization by cells. Cancer cells were grown in 2D or 3D and under a flow to evaluate the specificity of the targeted NA. Binding and internalization of the targeted NA were studied using flow cytometry, confocal microscopy and transmission electron microscopy. Results: We show that the targeted NA specifically bind to MSLN-expressing tumor cells. Moreover, such functionalized NA appear to be internalized more rapidly and in significantly larger proportions compared to naked ones in MSLN+ MPM cells, thereby demonstrating both the functionality and interest of the active targeting strategy. We demonstrated that targeted NA are mainly internalized through a clathrin-independent/dynamin-dependent endocytosis pathway and are directed to lysosomes for degradation. A 3D cell culture model based on MSLN-expressing multicellular tumor spheroids reveals NA penetration in the first superficial layers. Conclusion: Altogether, these results open the path to novel anticancer strategies based on MSLN-activated internalization of NA incorporating drugs to promote specific accumulation of active treatments in tumors.

Impact of RAFT chain transfer agents on the polymeric shell density of magneto-fluorescent nanoparticles and their cellular uptake.

The impact of nanoparticle surface chemistry on cell interactions and especially cell uptake has become evident over the last few years in nanomedicine. Since PEG polymers have proved to be ideal tools for attaining stealthiness and favor escape from the in vivo mononuclear phagocytotic system, the accurate control of their geometry is of primary importance and can be achieved through reversible addition-fragmentation transfer (RAFT) polymerization. In this study, we demonstrate that the residual groups of the chain transfer agents (CTAs) introduced in the main chain exert a significant impact on the cellular internalization of functionalized nanoparticles. High-resolution magic angle spinning 1H NMR spectroscopy and fluorescence spectroscopy permitted by the magneto-fluorescence properties of nanoassemblies (NAs) revealed the compaction of the PEG comb-like shell incorporating CTAs with a long alkyl chain, without changing the overall surface potential. As a consequence of the capability of alkyl units to self-assemble at the NA surface while hardly contributing more than 0.5% to the total polyelectrolyte weight, denser PEGylated NAs showed notably less internalization in all cells of the tumor microenvironment (tumor cells, macrophages and healthy cells). Interestingly, such differentiated uptake is also observed between pro-inflammatory M1-like and immunosuppressive M2-like macrophages, with the latter more efficiently phagocytizing NAs coated with a less compact PEGylated shell. In contrast, the NA diffusion inside multicellular spheroids, used to mimic solid tumors, appeared to be independent of the NA coating. These results provide a novel effort-saving approach where the sole variation of the chemical nature of CTAs in RAFT PEGylated polymers strikingly modulate the cell uptake of nanoparticles upon the organization of their surface coating and open the pathway toward selectively addressing macrophage populations for cancer immunotherapy.

Influence of the mechanical and geometrical parameters on the cellular uptake of nanoparticles: A stochastic approach.

Nanoparticles (NPs) are used for drug delivery with enhanced selectivity and reduced side-effect toxicity in cancer treatments. Based on the literature, the influence of the NPs mechanical and geometrical properties on their cellular uptake has been studied through experimental investigations. However, due to the difficulty to vary the parameters independently in such a complex system, it remains hard to efficiently conclude on the influence of each one of them on the cellular internalization of a NP. In this context, different mechanical / mathematical models for the cellular uptake of NPs have been developed. In this paper, we numerically investigate the influence of the NP's aspect ratio, the membrane tension and the cell-NP adhesion on the uptake of the NP using the model introduced in1 coupled with a numerical stochastic scheme to measure the weight of each one of the aforementioned parameters. The results reveal that the aspect ratio of the particle is the most influential parameter on the wrapping of the particle by the cell membrane. Then the adhesion contributes twice as much as the membrane tension. Our numerical results match the previous experimental observations.

Microfluidic Assisted Flash Precipitation of Photocrosslinkable Fluorescent Organic Nanoparticles for Fine Size Tuning and Enhanced Photoinduced Processes.

Highly concentrated dispersions of fluorescent organic nanoparticles (FONs), broadly used for optical tracking, bioimaging and drug delivery monitoring, are obtained using a newly designed micromixer chamber involving high impacting flows. Fine size tuning and narrow size distributions are easily obtained by varying independently the flow rates of the injected fluids and the concentration of the dye stock solution. The flash nanoprecipitation process employed herein is successfully applied to the fabrication of bicomposite FONs designed to allow energy transfer. Considerable enhancement of the emission signal of the energy acceptors is promoted and its origin is found to result from polarity rather than steric effects. Finally, we exploit the high spatial confinement encountered in FONs and their ability to encapsulate hydrophobic photosensitizers to induce photocrosslinking. An increase in the photocrosslinked FON stiffness is evidenced by measuring the elastic modulus at the nanoscale using atomic force microscopy. These results pave the way toward the straightforward fabrication of multifunctional and mechanically photoswitchable FONs, opening novel opportunities in sensing, multimodal imaging, and theranostics.

Coating Effect on the 1H-NMR Relaxation Properties of Iron Oxide Magnetic Nanoparticles.

We present a 1H Nuclear Magnetic Resonance (NMR) relaxometry experimental investigation of two series of magnetic nanoparticles, constituted of a maghemite core with a mean diameter dTEM = 17 ± 2.5 nm and 8 ± 0.4 nm, respectively, and coated with four different negative polyelectrolytes. A full structural, morpho-dimensional and magnetic characterization was performed by means of Transmission Electron Microscopy, Atomic Force Microscopy and DC magnetometry. The magnetization curves showed that the investigated nanoparticles displayed a different approach to the saturation depending on the coatings, the less steep ones being those of the two samples coated with P(MAA-stat-MAPEG), suggesting the possibility of slightly different local magnetic disorders induced by the presence of the various polyelectrolytes on the particles' surface. For each series, 1H NMR relaxivities were found to depend very slightly on the surface coating. We observed a higher transverse nuclear relaxivity, r2, at all investigated frequencies (10 kHz ≤ νL ≤ 60 MHz) for the larger diameter series, and a very different frequency behavior for the longitudinal nuclear relaxivity, r1, between the two series. In particular, the first one (dTEM = 17 nm) displayed an anomalous increase of r1 toward the lowest frequencies, possibly due to high magnetic anisotropy together with spin disorder effects. The other series (dTEM = 8 nm) displayed a r1 vs. νL behavior that can be described by the Roch's heuristic model. The fitting procedure provided the distance of the minimum approach and the value of the Néel reversal time (τ ≈ 3.5 ÷ 3.9·10-9 s) at room temperature, confirming the superparamagnetic nature of these compounds.

Hybrid Azo-fluorophore Organic Nanoparticles as Emissive Turn-on Probes for Cellular Endocytosis.

The development of fluorescent organic nanoparticles, serving as bioimaging agents or drug cargos, represents a buoyant field of investigations. Nevertheless, their ulterior fate and structural integrity after cell uptake remain elusive. Toward this aim, we have elaborated original photoactive organic nanoparticles (dTEM ∼ 35-50 nm wide) with an off-on signal upon cellular internalization. Such nanoparticles are based on the noncovalent association of red-emitting benzothiadiazole (BDZ) derivatives and azo dyes, acting as fluorescence quenchers. Upon varying the azo/BDZ ratio, we found that quantitative emission quenching could be obtained with only a 0.2:1 azo/BDZ ratio and originated from exergonic oxidative and reductive photoinduced electron transfer from the azo units (ΔelG0 = -0.21 and -0.29 eV, respectively). Such results revisited the origin of emission quenching, often confusedly ascribed to Förster resonance energy transfer. A nonlinear and sharp drop of the emission intensity with the increase in the azo unit density n was observed and presents comparable evolution to a n-1/3 mathematical law. Thorough biological examinations involving cancer cells prove a receptor-independent endocytosis pathway, leading to progressive cell lighting upon nanoparticle accumulation in the late endosomal/lysosomal compartments. Complete emission recovery of the initially quenched azo/BDZ nanosystems could be achieved by using mefloquine, which caused endosomal/lysosomal disruption, and release of their content in the cytoplasm. Such results demonstrate that the dotlike emission from endosomes actually stems from fully dissociated individual dyes and not integer nanoparticles. They conclude on the high spatial confinement promoted by organelles and finally question its severe impact on functional compounds or nanoparticles whose properties are strongly distance dependent.

Small Molecule-Based Fluorescent Organic Nanoassemblies with Strong Hydrogen Bonding Networks for Fine Tuning and Monitoring Drug Delivery in Cancer Cells.

Bright supramolecular fluorescent organic nanoassemblies (FONs), based on strongly polar red-emissive benzothiadiazole fluorophores containing acidic units, are fabricated to serve as theranostic tools with large colloidal stability in the absence of a polymer or surfactant. High architectural cohesion is ensured by the multiple hydrogen-bonding networks, reinforced by the dipolar and hydrophobic interactions developed between the dyes. Such interactions are harnessed to ensure high payload encapsulation and efficient trapping of hydrophobic and hydrogen-bonding drugs like doxorubicin, as shown by steady state and time-resolved measurements. Fine tuning of the drug release in cancer cells is achieved by adjusting the structure and combination of the fluorophore acidic units. Notably delayed drug delivery is observed by confocal microscopy compared to the entrance of hydrosoluble doxorubicin, demonstrating the absence of undesirable burst release outside the cells by using FONs. Since FON-constituting fluorophores exhibit a large emission shift from red to green when dissociating in contact with the lipid cellular content, drug delivery could advantageously be followed by dual-color spectral detection, independently of the drug staining potentiality.

Bioconjugated fluorescent organic nanoparticles targeting EGFR-overexpressing cancer cells.

The field of optical bioimaging has considerably flourished with the advent of sophisticated microscopy techniques and ultra-bright fluorescent tools. Fluorescent organic nanoparticles (FONs) have thus recently appeared as very attractive labels for their high payload, absence of cytotoxicity and eventual biodegradation. Nevertheless, their bioconjugation to target specific receptors with high imaging contrast is scarcely performed. Moreover, assessing the reality of bioconjugation represents high challenges given the sub-nanomolar concentrations resulting from the commonly adopted nanoprecipitation fabrication process. Here, we describe how the combination of a magnetic shell allows us to easily generate red-emitting FONs conjugated with the epidermal growth factor ligand (EGF), a small protein promoting cancer cell proliferation by activating the EGF receptor (EGFR) pathway. Dual color fluorescence correlation spectroscopy combined with immunofluorescence is originally harnessed in its time trace mode to unambiguously demonstrate covalent attachment between the FON and EGF at sub-nanomolar concentrations. Strong asymmetric clustering of EGF-conjugated FONs is observed at the membrane of MDA-MB-468 human breast cancer cells overexpressing EGF receptors using super-resolution fluorescence microscopy. Such high recruitment of EGF-conjugated FONs is attributed to their EGF multivalency (4.7 EGF per FON) which enables efficient EGFR activation and subsequent phosphorylation. The large hydrodynamic diameter (DH ∼ 301 nm) of EGF-conjugated FONs prevents immediate engulfment of the sequestered receptors, which provides very bright and localized spots in less than 30 minutes. The reported bioconjugated nanoassemblies could thus serve as ultra-bright probes of breast cancer cells with EGFR-overexpression that is often associated with poor prognosis.

PEGylated Anionic Magnetofluorescent Nanoassemblies: Impact of Their Interface Structure on Magnetic Resonance Imaging Contrast and Cellular Uptake.

Controlling the interactions of functional nanostructures with water and biological media represents high challenges in the field of bioimaging applications. Large contrast at low doses, high colloidal stability in physiological conditions, the absence of cell cytotoxicity, and efficient cell internalization represent strong additional needs. To achieve such requirements, we report on high-payload magnetofluorescent architectures made of a shell of superparamagnetic iron oxide nanoparticles tightly anchored around fluorescent organic nanoparticles. Their external coating is simply modulated using anionic polyelectrolytes in a final step to provide efficient magnetic resonance imaging (MRI) and fluorescence imaging of live cells. Various structures of PEGylated polyelectrolytes have been synthesized and investigated, differing from their iron oxide complexing units (carboxylic vs phosphonic acid), their structure (block- or comblike), their hydrophobicity, and their fabrication process [conventional or reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization] while keeping the central magnetofluorescent platforms the same. Combined photophysical, magnetic, NMRD, and structural investigations proved the superiority of RAFT polymer coatings containing carboxylate units and a hydrophobic tail to impart the magnetic nanoassemblies (NAs) with enhanced-MRI negative contrast, characterized by a high r2/r1 ratio and a transverse relaxation r2 equal to 21 and 125 s-1 mmol-1 L, respectively, at 60 MHz clinical frequency (∼1.5 T). Thanks to their dual modality, cell internalization of the NAs in mesothelioma cancer cells could be evidenced by both confocal fluorescence microscopy and magnetophoresis. A 72 h follow-up showed efficient uptake after 24 h with no notable cell mortality. These studies again pointed out the distinct behavior of RAFT polyelectrolyte-coated bimodal NAs that internalize at a slower rate with no adverse cytotoxicity. Extension to multicellular tumor cell spheroids that mimic solid tumors revealed the successful internalization of the NAs in the periphery cells, which provides efficient deep-imaging labels thanks to their induced T2* contrast, large emission Stokes shift, and bright dotlike signal, popping out of the strong spheroid autofluorescence.

Tuning the architectural integrity of high-performance magneto-fluorescent core-shell nanoassemblies in cancer cells.

High-density nanoarchitectures, endowed with simultaneous fluorescence and contrast properties for MRI and TEM imaging, have been obtained using a simple self-assembling strategy based on supramolecular interactions between non-doped fluorescent organic nanoparticles (FON) and superparamagnetic nanoparticles. In this way, a high-payload core-shell structure FON@mag has been obtained, protecting the hydrophobic fluorophores from the surroundings as well as from emission quenching by the shell of magnetic nanoparticles. Compared to isolated nanoparticles, maghemite nanoparticles self-assembled as an external shell create large inhomogeneous magnetic field, which causes enhanced transverse relaxivity and exacerbated MRI contrast. The magnetic load of the resulting nanoassemblies is evaluated using magnetic sedimentation and more originally electrospray mass spectrometry. The role of the stabilizing agents (citrate versus polyacrylate anions) revealed to be crucial regarding the cohesion of the resulting high-performance magneto-fluorescent nanoassemblies, which questions their use after cell internalization as nanocarriers or imaging agents for reliable correlative light and electron microcopy.

All-Solution-Processed Organic Light-Emitting Diodes Based on Photostable Photo-cross-linkable Fluorescent Small Molecules.

We demonstrate herein the fabrication of small molecule-based OLEDs where four organic layers from the hole- to the electron-transporting layers have successively been deposited by using an all-solution process. The key feature of the device relies on a novel photopolymerizable red-emitting material, made of small fluorophores substituted with two acrylate units, and displaying high-quality film-forming properties as well as high emission quantum yield as nondoped thin films. Insoluble emissive layers were obtained upon UV irradiation using low illumination doses, with no further need of postcuring. Very low photodegradation was noticed, giving rise to bright layers with a remarkable surface quality, characterized by a mean RMS roughness as low as 0.7 nm after development. Comparative experiments between solution-processed OLEDs and vacuum-processed OLEDs made of fluorophores with close architectures show external quantum efficiencies in the same range while displaying distinct behaviors in terms of current and power efficiencies. They validate the proof of concept of nondoped solution-processable emissive layers exclusively made of photopolymerized fluorophores, thereby reducing the amount of components and opening the way toward cost-effective fabrication of solution-processed OLED multilayer architectures.

Pro-osteoclastic in vitro effect of Polyethylene-like nanoparticles: Involvement in the pathogenesis of implant aseptic loosening.

Polyethylene micro-sized wear particles released from orthopedic implants promote inflammation and osteolysis; however, less is known about the bioactivity of polyethylene nanosized wear particles released from the last generation of polymer-bearing surfaces. We aim to assess the internalization of fluorescent polyethylene-like nanoparticles by both human macrophages and osteoclasts and also, to determine their effects in osteoclastogenesis in vitro. Human macrophages and osteoclasts were incubated with several ratios of fluorescent polyethylene-like nanoparticles between 1 and 72 h, and 4 h, 2, 4, 6, and 9 days, respectively. The internalization of nanoparticles was quantified by flow cytometry and followed by both confocal and video time-lapse microscopy. Osteoclast differentiation and activity was semiquantified by tartrate-resistant acid phosphatase (TRAP) staining, TRAP mRNA relative expression, and pit resorption assay, respectively. Macrophages, osteoclast precursors and mature osteoclasts internalized nanoparticles in a dose- and time-dependent manner and maintained their resorptive activity. In addition, nanoparticles significantly increased the osteoclastogenesis as shown by upregulation of the TRAP expressing cell number. We conclude that polyethylene-like nanosized wear particles promote osteoclast differentiation without alteration of bone resorptive activity of mature osteoclasts and they could be considered as important actors in periprosthetic osteolysis of the last new generation of polymer-bearing surfaces. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2649-2657, 2016.

Are Fluorescent Organic Nanoparticles Relevant Tools for Tracking Cancer Cells or Macrophages?

Strongly solvatochromic fluorophores are devised, containing alkyl chains and enable to self-assemble as very bright fluorescent organic nanoparticles (FONs) in water (Φf = 0.28). The alkyl chains impart each fluorophore with strongly hydrophobic surroundings, causing distinct emission colors between FONs where the fluorophores are associated, and their disassembled state. Such color change is harnessed to assess the long-term fate of FONs in both cancer cells and monocytes/macrophages. Disintegration of the orange-emitting FONs by monocytes/macrophages is evidenced through the formation of micrometer green-yellowish emitting vesicles. By contrast, cancer cells retain longer the integrity of organic nanoparticles. In both cases, no significant toxicity is detected, making FONs as valuable bioimaging agents for cell tracking with weak risks of deleterious accumulation and low degradation rate.

Enhanced Rates of Photoinduced Molecular Orientation in a Series of Molecular Glassy Thin Films.

Photoinduced orientation in a series of molecular glasses made of small push-pull azo derivatives is dynamically investigated for the first time. Birefringence measurements at 632.8 nm are conducted with a temporal resolution of 100 ms to probe the fast rate of the azo orientation induced under polarized light and its temporal stability over several consecutive cycles. To better evaluate the influence of the azo chemical substituents and their electronic properties on the orientation of the whole molecule, a series of push-pull azo derivatives involving a triphenylaminoazo core substituted with distinct electron-withdrawing moieties is studied. All resulting thin films are probed using polarization modulation infrared spectroscopy that yields dynamical linear dichroism measurements during a cycle of orientation followed by relaxation. We show here in particular that the orientation rates of small molecule-based azo materials are systematically increased up to 7-fold compared to those of a reference polymer counterpart. For specific compounds, the percentage of remnant orientation is also higher, which makes these materials of great interest and promising alternatives to azobenzene-containing polymers for a variety of applications requiring a fast response and absolute control over the molecular weight.

Photochromic organic nanoparticles as innovative platforms for plasmonic nanoassemblies.

The fabrication of hybrid core-shell nanoassemblies involving a nondoped azo photochromic core coated with a dense shell of gold nanoparticles is reported to investigate the influence of localized plasmons onto the azo core photoisomerization. Photochromic organic nanoparticles, regarded as a novel class of high-density photoswitchable nanomaterials, are first elaborated upon precipitation in water of push-pull azo molecules, containing sulfur-terminated units to chelate gold nanoparticles. Photoisomerization studies of the azo nanoparticles reveal significantly higher E → Z photoconversion yields and Z → E thermal back relaxation rate constants compared to those of dyes processed as thin films and in solution, respectively. These unexpected results are ascribed to the large surface-to-volume ratio and cooperative effects encountered in nanoparticles that deform without disassembling under polarized illumination as a result of the weak change in the azo dipole moment. UV-vis spectroscopy and Raman microscopy of the hybrid nanoassemblies show strong optical coupling between both photoactive constituents, confirming that gold nanoparticles are tightly positioned on the azo core surface. Such coupling causes partial quenching of the azo photoisomerization but does not impact the thermal back relaxation. Longer sulfur-terminated chains provide reduced quenching of the photoreaction by the localized plasmons, thereby opening perspectives toward plasmon-mediated deformation of nano-objects for light-controlled nanomechanics.

Molecular structure-optical property relationships for a series of non-centrosymmetric two-photon absorbing push-pull triarylamine molecules.

This article reports on a comprehensive study of the two-photon absorption (2PA) properties of six novel push-pull octupolar triarylamine compounds as a function of the nature of the electron-withdrawing groups. These compounds present an octupolar structure consisting of a triarylamine core bearing two 3,3'-bis(trifluoromethyl)phenyl arms and a third group with varying electron-withdrawing strength (H < CN < CHO < NO2 < Cyet < Vin). The 2PA cross-sections, measured by using the femtosecond open-aperture Z-scan technique, showed significant enhancement from 45 up to 125 GM for the lowest energy band and from 95 up to 270 GM for the highest energy band. The results were elucidated based on the large changes in the transition and permanent dipole moments and in terms of (i) EWG strength, (ii) degree of donor-acceptor charge transfer and (iii) electronic coupling between the arms. The 2PA results were eventually supported and confronted with theoretical DFT calculations of the two-photon transition oscillator strengths.

Nanoparticle organization through photoinduced bulk mass transfer.

A series of dipolar triphenylaminoazo derivatives, with largely distinct charge transfer and glass transition temperatures, has been synthesized. Their photomigration capability in the solid state to form surface relief gratings (SRGs) under interferential illumination has been investigated with respect to their photochromic properties and showed a prevailing influence of the bulkiness of the azo substituent. The azo mass transfer was utilized to efficiently photoalign 200 nm polystyrene nanoparticles along the SRG crests, which were initially deposited on nonirradiated azo surfaces. In contrast, nanoparticles spin cast on prestructured surface relief gratings were localized in the troughs of the periodic structures. These distinct locations point out the ability of isotropic and amorphous photochromic thin films to collectively move and organize nano-objects in an ordered fashion through the use of polarized illumination. This versatile approach opens the path to optically aligned ensembles of individual nano-objects over large areas, which can be further combined with metallic conductive or magnetic coating to create novel functional nanostructures.

Highly cohesive dual nanoassemblies for complementary multiscale bioimaging.

Innovative nanostructures made of a high payload of fluorophores and superparamagnetic nanoparticles (NPs) have simply been fabricated upon self-assembling in a two-step process. The resulting hybrid supraparticles displayed a dense shell of iron oxide nanoparticles tightly attached through an appropriate polyelectrolyte to a highly emissive non-doped nanocore made of more than 105 small organic molecules. Cooperative magnetic dipole interactions arose due to the closely packed magnetic NPs at the nanoarchitecture surface, causing enhanced NMR transverse relaxivity. Large in vivo MRI T2 contrast was thus obtained with unusually diluted solutions after intravenous injection in small rodents. Two-photon excited fluorescence imaging could be performed, achieving unprecedented location resolution for agents combining both magnetic nanoparticles and fluorescence properties. Finally, TEM imaging of the sectioned mouse tissue succeeded in isolating the core-shell structures, which represents the first image of intact complex magnetic and fluorescent nanoassemblies upon in vivo injection. Such highly cohesive dual nanoarchitectures should open great horizons toward the assessment with high spatial resolution of the drug or labeled stem cell biodistribution.

Comprehensive investigation of the excited-state dynamics of push-pull triphenylamine dyes as models for photonic applications.

A series of emitting push-pull triarylamine derivatives, models of their widely used homologues in photonics and organic electronics, was investigated by steady-state and time-resolved spectroscopy. Their structural originality stems from the sole change of the electron-withdrawing substituent X (-H: 1, -CN: 2, -NO2: 3, -CHC(CN)2: 4), giving rise to efficient emission tuning from blue to red upon increasing the X electron-withdrawing character. All compounds are highly fluorescent in alkanes. The more polar compounds 2-4 undergo considerable Stokes shift and emission quenching in polar solvents. Femtosecond transient absorption data allowed us to identify the nature of the emissive state which varies as a function of the compound and surrounding polarity. A long-lived ππ* excited state with weak charge transfer character was found for 1. This excited state evolves into a long-lived ICT state with red-shifted emission for 2 in polar solvents. For 3 and 4, the ICT state is directly populated in all solvents. Long-lived and emissive in n-hexane, it relaxes in toluene to a new ICT' conformation with stronger charge transfer character and enhanced Stokes shift. In more polar THF, ethanol, and nitrile solvents, ICT relaxes to a dark excited state ICT'' with viscosity-dependent kinetics (<10 ps). The ICT'' state lifetime drops with increasing solvent polarity (150 ps for 3 in THF, 8.5 ps in butyronitrile, 1.9 ps in acetonitrile), denoting an efficient radiationless deactivation to the ground state (back charge transfer). This result reveals a very small S0-S1 energy gap at the relaxed ICT'' geometry, with a possible close-lying S0-S1 conical intersection, which suggests that the ICT → ICT'' process results from a structural change involving a large-amplitude molecular distortion. This fast structural change can account for the strong fluorescence quenching observed for 3 and 4 in polar solvents. Finally, the magnitude of intersystem crossing between the singlet and triplet excited states largely depends on the electron-deficient X unit and the solvent itself. These observations help one conclude on the prevailing role played by the electron-withdrawing groups and the surrounding polarity in the photophysical performances of triphenylamine derivatives, largely employed in numerous emissive solid-state devices.