Vincent Hugues

Two‐Photon‐Triggered Drug Delivery via Fluorescent Nanovalves

Mesoporous silica nanoparticles (MSN) are functionalized in the walls with an original fluorophore with a high two-photon absorption cross-section. The pores of the MSN filled with anticancer drug are blocked with a pseudo-rotaxane constituted by an azobenzene stalk and a β-cyclodextrin moiety. After incubation of the nanosystem with MCF-7 breast cancer cells, two-photon irradiation at low power is used to image the cells. At high power, cancer cell killing is observed due to the two-photon-triggered opening of the pores through FRET and the release of the anticancer drug from the MSN.

Two‐Photon Excitation of Porphyrin‐Functionalized Porous Silicon Nanoparticles for Photodynamic Therapy

Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect.

Bright, emission tunable fluorescent dyes based on imidazole and π-expanded imidazole

A diverse set of imidazole- and π-expanded imidazole derivatives displaying excited state intramolecular proton transfer (ESIPT) was designed and synthesized. The effect of structural variation on photophysical properties was studied in detail for nine dyes. The relationship between the structure and photophysical properties was thoroughly elucidated also by comparing with analogues with blocked ESIPT functionality. All but one of the obtained compounds exhibit ESIPT, as demonstrated by large Stokes shifts (6500–15 600 cm−1). The type of π-expansion strongly influences the overall optical phenomena: while typical π-expansion preserves ESIPT activity, the direct fusion of imidazole with a naphthalene unit at positions 4 and 5 results in dyes which do not exhibit ESIPT. The compound possessing an acidic NH group as part of an intramolecular hydrogen bond system has a much higher fluorescence quantum yield and Stokes shift than its analogue bearing an OH group. The occurrence of ESIPT for tosylamide analogues is less affected by the hydrogen-bonding ability of the solvents compared to the unprotected amines. Two-photon absorption cross-sections of the selected derivatives are in the range of 5–100 GM.

Octupolar merocyanine dyes: a new class of nonlinear optical chromophores.

A set of new octupolar merocyanine chromophores was designed and synthesized. These compounds were prepared from the reaction of 1,3,5-triformyl-2,4,6-trihydroxybenzene with heterocyclic nucleophiles. Octupolar dyes were formed exclusively in their open-dye form. The one- and two-photon-absorption spectra of the dyes consist of two bands: The long-wavelength band in the two-photon absorption spectrum (a few hundreds GM above 1000 nm) matches well with the intense, long-wavelength-absorption band that is located in the visible region in the linear spectrum. Interestingly, an additional, much-more-intense TPA band in the NIR region is observed at higher energy, which corresponds to a weakly allowed one-photon electronic transition. Changing the peripheral heterocyclic moieties allows tuning of the optical properties to approach the cyanine limit (i.e., polymethine state), thus resulting in a red-shift of the low-energy one-photon-absorption band as well as to the rise of an intense two-photon-absorption band in the NIR region. To the best of our knowledge, this is the first synthesis and TPA characterization of octupolar merocyanine chromophores with typical low-bond-length alternation.

Enhanced Two‐Photon Fluorescence Imaging and Therapy of Cancer Cells via Gold@Bridged Silsesquioxane Nanoparticles

A two-photon photosensitizer with four triethoxysilyl groups is synthesized through the click reaction. This photosensitizer allows the design of bridged silsesquioxane (BS) nanoparticles through a sol-gel process; moreover, gold core BS shells or BS nanoparticles decorated with gold nanospheres are synthesized. An enhancement of the two-photon properties is noted with gold and the nanoparticles are efficient for two-photon imaging and two-photon photodynamic therapy of cancer cells.

Polar Diketopyrrolopyrrole‐Imidazolium Salts as Selective Probes for Staining Mitochondria in Two‐Photon Fluorescence Microscopy

Three rationally designed polar derivatives of diketopyrrolopyrrole consisting of 1,3-dimethylimidazolium cationic units and benzene, thiophene, or furan rings as π spacers were synthesized and thoroughly studied. The obtained salts are soluble in polar organic solvents and show satisfactory solubility in water, which makes them suitable for the applications in bioimaging. Photophysical measurements revealed that the obtained derivatives are characterized by strong absorption and good fluorescence quantum yields. The corresponding two-photon properties were also examined and showed that the synthesized salts exhibit large two-photon absorption cross-sections reaching 4000 GM (GM=Goeppert-Mayer unit, 1 GM=10(-50)  cm(4)  s photon(-1) ) and very high two-photon brightness values exceeding 2000 GM. It was demonstrated that these salts can be safely applied in two-photon fluorescence microscopy for selective staining of mitochondria in living cells.

Two‐Photon‐Induced Fluorescence in New π‐Expanded Diketopyrrolopyrroles

Structurally unique π-expanded diketopyrrolopyrroles (EDPP) were designed and synthesized. Strategic placement of a fluorene scaffold at the periphery of a diketopyrrolopyrrole through tandem Friedel-Crafts-dehydration reactions resulted in dyes with supreme solubility. The structure of the dyes was confirmed by X-ray crystallography verifying a nearly flattened arrangement of the ten fused rings. Despite the extended ring system, the dye still preserved good solubility and was further functionalized by using Pd-catalyzed coupling reactions, such as the Buchwald-Hartwig amination. Photophysical studies of these new functional dyes revealed that they possess enhanced properties when compared with expanded DPPs in terms of two-photon absorption cross-section. It is further demonstrated that in addition to the initial diacetals, the final electrophilic cyclization step can also be applied to diketones. By placing two amine groups at peripheral positions of the resulting dyes, values of two-photon absorption cross-section on the level of 2000 GM around 1000 nm were achieved, which in combination with high fluorescence quantum yield (Φfl ), generated a two-photon brightness of approximately 1600 GM. These characteristics in combination with strong red emission (665 nm) make these new π-expanded diketopyrrolopyrroles of major promise as two-photon dyes for bioimaging applications. Finally, the corresponding N-alkylated DPPs displayed a solid-state fluorescence.

Bright, fluorescent dyes based on imidazo[1,2-a]pyridines that are capable of two-photon absorption.

A library of imidazo[1,2-a]pyridines was synthesized by using the Gevorgyan method and their linear and non-linear optical properties were studied. Derivatives that contained both electron-donating and electron-withdrawing groups at the 2 position were comprehensively investigated. Their emission quantum yield ranged between 0.2-0.7 and it was shown to depend on the substitution pattern, most notably that on the phenyl ring. Electron-donating substituents improved the luminescence performance of these compounds, whereas electron-withdrawing substituents led to a more erratic behavior. Substitution on the six-membered ring had less effect on the fluorescence properties. Extension of the delocalization increased the luminescence quantum yield. A new quadrupolar system was designed that contained two imidazo[1,2-a]pyridine units on its periphery and a 1,4-dicyanobenzene unit at its center. This system exhibited a large Stokes-shifted luminescence that was affected by the polarity and rigidity of the solvent, which was ascribed to emission from an excited state with strong charge-transfer character. This quadrupolar feature also led to an acceptable two-photon absorption response in the NIR region.

Disulfide-gated mesoporous silica nanoparticles designed for two-photon-triggered drug release and imaging

We report a two-photon-actuated cancer cell killing system that kills the cancer cells via drug delivery through multifunctional mesoporous silica nanogates. Two-photon-sensitive mesoporous organosilica (M2PS) nanocarriers were synthesized via the co-condensation of a silica precursor and a two-photon electron donor. The nanogates were constructed using a fast one-pot process at room temperature on the drug-loaded M2PS nanoparticles (NPs) with the bis(3-triethoxysilylpropyl)disulfide precursor. One and two-photon-actuated cargo releases from the M2PS nanogates were successfully monitored in aqueous solutions. Furthermore, the cellular uptake in MCF-7 cells was demonstrated via two-photon fluorescence imaging of the NPs, which were then applied successfully for drug delivery in cells.

Fluorescence and two-photon absorption of push–pull aryl(bi)thiophenes: structure–property relationships

Photophysical and TPA properties of series of push-pull aryl(bi)thiophene chromophores bearing electron-donating (D) and electron-withdrawing (A) end-groups of increasing strength are presented. All compounds show an intense intramolecular charge transfer (ICT) absorption band in the visible region. Increasing the D and/or A strength as well as the length of the conjugated path induces bathochromic and hyperchromic shifts of the absorption band as reported for analogous push-pull polyenes. Yet, in contrast with corresponding push-pull polyenes, a significant increase in fluorescence is observed. In particular, chromophores built from a phenyl-bithienyl conjugated path and bearing strong D and A end-groups were found to combine very large one and two-photon brightness as well as strong emission in the red/NIR region. These molecules hold promise as biphotonic fluorescent probes for bioimaging.