Infrared and Raman spectroscopy of non-conventional hydrogen bonding between N,N'-disubstituted urea and thiourea groups: a combined experimental and theoretical investigation.

The variety of H bond (HB) interactions is a source of inspiration for bottom-up molecular engineering through self-aggregation. Non-conventional intermolecular HBs between N,N'-disubstituted urea and thiourea are studied in detail by vibrational spectroscopies and ab initio calculations. Raman and IR mode assignments are given. We show that it is possible to study selectively the different intermolecular bifurcated intra- and inter-dimer HBs with the two types of HB acceptors. Through the ab initio calculation, the thioamide I mode, a specific marker of N-HS[double bond, length as m-dash]C HB interactions, is unambiguously identified.

Porphyrin-based bridged silsesquioxane nanoparticles for targeted two-photon photodynamic therapy of zebrafish xenografted with human tumor.

BACKGROUND: Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine. AIMS: In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small-sized nanoparticles were functionalized with PEG and mannose (PORBSNs-mannose) in order to target breast tumors in vivo. METHODS AND RESULTS: The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two-photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs-mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two-photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation. CONCLUSION: We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs-mannose injected in the blood stream of zebrafish xenografted with human tumors.

Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles for two-photon photodynamic therapy or photoacoustic imaging.

Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles (BSPOR and BSPHT) were prepared. Their endocytosis in MCF-7 cancer cells was shown with two-photon excited fluorescence (TPEF) imaging. With two-photon excited photodynamic therapy (TPE-PDT), BSPOR was more phototoxic than BSPHT, which in contrast displayed a very high signal for photoacoustic imaging in mice.

Organosilica hybrid nanomaterials with a high organic content: syntheses and applications of silsesquioxanes.

Organic-inorganic hybrid materials garner properties from their organic and inorganic matrices as well as synergistic features, and therefore have recently attracted much attention at the nanoscale. Non-porous organosilica hybrid nanomaterials with a high organic content such as silsesquioxanes (R-SiO1.5, with R organic groups) and bridged silsesquioxanes (O1.5Si-R-SiO1.5) are especially attractive hybrids since they provide 20 to 80 weight percent of organic functional groups in addition to the known chemistry and stability of silica. In the organosilica family, silsesquioxanes (R-SiO1.5) stand between silicas (SiO2) and silicones (R2SiO), and are variously called organosilicas, ormosil (organically-modified silica), polysilsesquioxanes and silica hybrids. Herein, we comprehensively review non-porous silsesquioxane and bridged silsesquioxane nanomaterials and their applications in nanomedicine, electro-optics, and catalysis.

Bis-clickable Mesoporous Silica Nanoparticles: Straightforward Preparation of Light-Actuated Nanomachines for Controlled Drug Delivery with Active Targeting.

Bis(clickable) mesoporous silica nanospheres (ca. 100 nm) were obtained by the co-condensation of TEOS with variable amounts (2-5 % each) of two clickable organosilanes in the presence of CTAB. Such nanoparticles could be easily functionalized with two independent functions using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction to transform them into nanomachines bearing cancer cell targeting ligands with the ability to deliver drugs on-demand. The active targeting was made possible after anchoring folic acid by CuAAC click reaction, whereas the controlled delivery was performed by clicked azobenzene fragments. Indeed, the azobenzene groups are able to obstruct the pores of the nanoparticles in the dark whereas upon irradiation in the UV or in the blue range, their trans-to-cis photoisomerization provokes disorder in the pores, enabling the delivery of the cargo molecules. The on-command delivery was proven in solution by dye release experiments, and in vitro by doxorubicin delivery. The added value of the folic acid ligand was clearly evidenced by the difference of cell killing induced by doxorubicin-loaded nanoparticles under blue irradiation, depending on whether the particles featured the clicked folic acid ligand or not.

Evaporation-induced self-structuring of organised silica nanohybrid films through cooperative physical and chemical interactions.

In this work, we develop the concept of evaporation-induced self-structuring as a novel approach for producing organised films by exploiting cooperative physical and chemical interactions under far-from-equilibrium conditions (spin-coating), using sol-gel precursors with multiple functional groups. Thin films of self-structured silsesquioxane nanohybrids have been deposited by spin coating through the sol-gel hydrolysis and condensation of a bridged organosilane bearing self-assembling urea groups. The resulting nanostructure, investigated by FTIR, AFM and SEM, is shown to be highly dependent on the catalyst used (nucleophilic or acidic), and can be further modulated by varying the spinning rate. FTIR studies revealed the presence of highly organised structures under acidic catalysis due to strong hydrogen bonding between urea groups and hydrophobic interactions between long alkylene chains. The preferential orientation of the urea cross-links parallel to the substrate is shown using polarized FTIR experiments.

Multifunctional Gold-Mesoporous Silica Nanocomposites for Enhanced Two-Photon Imaging and Therapy of Cancer Cells.

Three dimensional sub-micron resolution has made two-photon nanomedicine a very promising medical tool for cancer treatment since current techniques cause significant side effects for lack of spatial selectivity. Two-photon-excited (TPE) photodynamic therapy (PDT) has been achieved via mesoporous nanoscaffolds, but the efficiency of the treatment could still be improved. Herein, we demonstrate the enhancement of the treatment efficiency via gold-mesoporous organosilica nanocomposites for TPE-PDT in cancer cells when compared to mesoporous organosilica particles. We performed the first comparative study of the influence of the shape and spatial position of gold nanoparticles (AuNPs) with mesoporous silica nanoparticles (MSN) functionalized with thiol groups and doped with a two-photon electron donor (2PS). The resulting multifunctional nanocarriers displayed TPE-fluorescence and were imaged inside cells. Furthermore, mesoporous organosilica NPs decorated gold nanospheres (AuNSs) induced 63 percent of selective killing on MCF-7 breast cancer cells. This study thus provides insights for the design of more effective multifunctional two-photon-sensitive nanocomposites via AuNPs for biomedical applications.

Enhanced Collective Magnetic Properties in 2D Monolayers of Iron Oxide Nanoparticles Favored by Local Order and Local 1D Shape Anisotropy.

Magnetic nanoparticle arrays represent a very attractive research field because their collective properties can be efficiently modulated as a function of the structure of the assembly. Nevertheless, understanding the way dipolar interactions influence the intrinsic magnetic properties of nanoparticles still remains a great challenge. In this study, we report on the preparation of 2D assemblies of iron oxide nanoparticles as monolayers deposited onto substrates. Assemblies have been prepared by using the Langmuir-Blodgett technique and the SAM assisted assembling technique combined to CuAAC "click" reaction. These techniques afford to control the formation of well-defined monolayers of nanoparticles on large areas. The LB technique controls local ordering of nanoparticles, while adjusting the kinetics of CuAAC "click" reaction strongly affects the spatial arrangement of nanoparticles in monolayers. Fast kinetics favor disordered assemblies while slow kinetics favor the formation of chain-like structures. Such anisotropic assemblies are induced by dipolar interactions between nanoparticles as no magnetic field is applied and no solvent evaporation is performed. The collective magnetic properties of monolayers are studied as a function of average interparticle distance, local order and local shape anisotropy. We demonstrate that local control on spatial arrangement of nanoparticles in monolayers significantly strengthens dipolar interactions which enhances collective properties and results in possible super ferromagnetic order.

Fluorescent periodic mesoporous organosilica nanoparticles dual-functionalized via click chemistry for two-photon photodynamic therapy in cells.

The synthesis of ethenylene-based periodic mesoporous organosilica nanoparticles for two-photon imaging and photodynamic therapy of breast cancer cells is described. A dedicated two-photon absorbing fluorophore possessing four triethoxysilyl groups and having large two-photon absorption in the near IR region, and azidopropyltriethoxysilane were incorporated into the structure. The mesoporous nanoparticles of 100 nm diameter were further functionalized by means of click chemistry with a propargylated fluorescent bromo-quinoline photosensitizer able to generate singlet oxygen. The photophysical properties and two-photon absorption properties of the nanoparticles were investigated evidencing complementary contribution of the two dyes. Both dyes contribute to the two-photon absorption response of the mesoporous nanoparticles while efficient FRET from the two-photon fluorophore to the quinoline sensitizer is observed. The dual-functionalized nanoparticles were incubated with MCF-7 breast cancer cells. Two-photon confocal imaging demonstrated the endocytosis of the nanoparticles within cancer cells. Moreover, brief two-photon irradiation (3 scans of 1.57 s) at 760 nm at high laser power (3 W) was shown to induce 40% of cancer cell death demonstrating the potential of the dual-functionalized mesoporous organosilica nanoparticles for two-photon photodynamic therapy.

Syntheses and applications of periodic mesoporous organosilica nanoparticles.

Periodic Mesoporous Organosilica (PMO) nanomaterials are envisioned to be one of the most prolific subjects of research in the next decade. Similar to mesoporous silica nanoparticles (MSN), PMO nanoparticles (NPs) prepared from organo-bridged alkoxysilanes have tunable mesopores that could be utilized for many applications such as gas and molecule adsorption, catalysis, drug and gene delivery, electronics, and sensing; but unlike MSN, the diversity in chemical nature of the pore walls of such nanomaterials is theoretically unlimited. Thus, we expect that PMO NPs will attract considerable interest over the next decade. In this review, we will present a comprehensive overview of the synthetic strategies for the preparation of nanoscaled PMO materials, and then describe their applications in catalysis and nanomedicine. The remarkable assets of the PMO structure are also detailed, and insights are provided for the preparation of more complex PMO nanoplatforms.

Synthesis of disulfide-based biodegradable bridged silsesquioxane nanoparticles for two-photon imaging and therapy of cancer cells.

Biodegradable bridged silsesquioxane (BS) nanomaterials for two-photon-excited (TPE) imaging and therapy of breast cancer cells were described. A versatile synthesis was developed to design monodisperse tetra-alkoxysilylated diamino-diphenylbutadiene or Zn-porphyrin-based nanospheres of 30 to 50 nm.

Controlled multiple functionalization of mesoporous silica nanoparticles: homogeneous implementation of pairs of functionalities communicating through energy or proton transfers.

The synthesis of mesoporous silica nanoparticles bearing organic functionalities is strained by the careful adjustment of the reaction parameters, as the incorporation of functional and/or voluminous organosilanes during the sol-gel synthesis strongly affects the final structure of the nanoparticles. In this paper we describe the design of new clickable mesoporous silica nanoparticles as spheres or rods, synthesized by the co-condensation of TEOS with two clickable organosilanes (bearing alkyne and azide groups) and readily multi-functionalizable by CuAAC click chemistry. We show that controlled loadings of clickable functions can be homogeneously distributed within the MSN, allowing us to efficiently click-graft various pairs of functionalities while preserving the texture and morphology of the particles. The homogeneous distribution of the grafted functionalities was probed by FRET experiments between two anchored fluorophores. Moreover, a communication by proton transfer between two functions was demonstrated by constructing a light-actuated nanomachine that works through a proton transfer between a photoacid generator and a pH-sensitive supramolecular nanogate. The activation of the nanomachine enabled the successful release of rhodamine B in buffered solutions and the delivery of doxorubicin in breast cancer cells (MCF-7) upon blue irradiation.

Eu³âº-based bridged silsesquioxanes for transparent luminescent solar concentrators.

The sol-gel preparation of a bridged silsesquioxane containing europium(III) salts and 2-thenoyltrifluoroacetone has been achieved from a new ethane tetracarboxamide-based organosilane. Free-standing films with thicknesses up to 440 µm and maximum absolute quantum yield (q) of 0.34 ± 0.03 (excitation at 320 nm) were prepared by the drop cast method, while thin films (∼200-400 nm) spin-coated on glass substrates led to highly luminescent coatings with q = 0.60 ± 0.02 (excitation at 345 nm). The thin films were tested as planar luminescent solar concentrators and the optimized device displays an optical conversion efficiency of 12.3% in the absorbing spectral region of the active layer (300-380 nm).

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.

Influence of the synthetic method on the properties of two-photon-sensitive mesoporous silica nanoparticles.

Herein we report the modulation of the properties of mesoporous silica nanoparticles (NPs) via various synthetic approaches. Three types of elaborations were compared, one in aqueous media at 25 °C, and the other two at 80 °C in water or in a water-ethanol mixture. For all these methods, an alkoxysilylated two-photon photosensitizer (2PS) was co-condensed with tetraethylorthosilicate (TEOS) in the presence of cetyltrimethylammonium bromide (CTAB), leading to five two-photon-sensitive mesoporous silica (M2PS) NPs. The M2PS NP porous structure could be tuned from radial to worm-like and MCM-41 types of organization. Besides, the 2PS precursor spatial dispersion was found to be highly dependent on both the 2PS initial concentration and the elaboration process. As a result, two-photon properties were modulated by the choice of the synthesis, the best results being found in aqueous media at 25 or 80 °C. Finally, the M2PS NPs were used for in vitro two-photon imaging of cancer cells.

Porphyrin-functionalized mesoporous organosilica nanoparticles for two-photon imaging of cancer cells and drug delivery.

The synthesis of a zinc porphyrin derivative possessing eight triethoxysilyl groups was performed through a CuAAC-click reaction. This porphyrin was covalently entrapped in ethenylene-bridged mesoporous organosilica nanoparticles which efficiently allowed performing doxorubicin delivery and two-photon imaging of breast cancer cells.

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.

One-pot construction of multipodal hybrid periodic mesoporous organosilica nanoparticles with crystal-like architectures.

The design of hybrid multipodal PMO (mp-PMO) nanoparticles with crystal-like architectures elaborated in a one-pot, two-step process, involving the preparation of a benzene-based spherical PMO core followed by the formation of ethylene-based rod-shaped PMO pods on these cores is described.

Tailoring the hydrophilic/lipophilic balance of clickable mesoporous organosilicas by the copper-catalyzed azide-alkyne cycloaddition click-functionalization.

We have designed and synthesized a clickable bridged silsesquioxane material featuring pendant alkyne chains as an aggregate of golf-ball-like nanoparticles, as evidenced by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and small- and wide-angle X-ray scattering (SWAXS). Using the copper-catalyzed azide-alkyne cycloaddition reaction with a range of organic azides of variable characteristics, we transformed this parent bridged silsesquioxane into new materials with tunable hydrophilic/lipophilic balance in high conversions while preserving the original morphology. N2, cyclohexane, and water sorption experiments were used to quantify the affinity of these materials toward the sorbates through the determination of their Henry's constants. This resulted in the following hydrophilic scale: M-OH > M-PEG > M-C6 > M-Ph > M-F > M-C16, which was mostly confirmed by SWAXS measurements.

Biodegradable ethylene-bis(propyl)disulfide-based periodic mesoporous organosilica nanorods and nanospheres for efficient in-vitro drug delivery.

Periodic mesoporous organosilica nanorods and nanospheres are synthesized from 1,4-bis(triethoxysilyl)ethylene and bis(3-ethoxysilylpropyl)disulfide. The nanosystems present the long-range order of the hexagonal nanostructure. They are degraded in simulated physiological conditions. The loading and release of doxorubicin with these nanosystems are both pH dependent. These nanoparticles are endocytosed by breast cancer cells and are very efficient for doxorubicin delivery in these cells.