RESUMO
Herein, we report synthetic strategies for the development of a bifunctional Janus T4 tetrapod (Janus ring), in which the orthogonal silsesquioxane and organic faces are independently functionalized. An all-cis T4 tetrasilanolate was functionalized to introduce thiol moieties on the silsesquioxane face and naphthyl groups on the organic face to introduce luminescent and self-organization properties. The stepwise synthesis conditions required to prepare such perfectly defined oligomers via a suite of well-defined intermediates and to avoid polymerization or reactions over all eight positions of the tetrapod are explored via 29Si, 13C and 1H NMR, FTIR and TOF-ESI mass spectroscopy. To the best of our knowledge, this is one of the few reports of Janus T4 tetrapods, with different functional groups located on both faces of the molecule, thus expanding the potential range of applications for these versatile precursors.
Assuntos
Compostos de Sulfidrila , Polimerização , Espectroscopia de Ressonância MagnéticaRESUMO
The synthesis of multifunctional poly(amidoamine) (PAMAM)-based dendrimers containing a cleavable disulfide linker within each arm of the dendrimer, together with condensable triethoxysilyl groups on the periphery of the dendrimer, is described. The dendrimers were mixed with 1,4-bis(triethoxysilyl)benzene and subsequently transformed into silsesquioxane gels or periodic mesoporous organosilicas (PMOs) to generate materials with dendrimers covalently embedded within the interior of the silsesquioxane networks. Subsequent treatment of the gels with dithiothreitol enabled the core of the dendrimers to be selectively cleaved at the disulfide site, thus generating thiol functions localised within the pores. The effect of different dendrimer generations on the reactivity of the pendant thiol functions was probed by impregnation with gold salts, which were reduced to obtain gold nanoparticles within the pore networks of the gels and PMOs. The gels yielded polydisperse gold nanoparticles (2 to 70 nm) with dimensions modulated by the generation of the dendrimer, together with well-defined gold/thiolate clusters with Auâ¯S distances of 2.3 Å. Such clusters were also observed in the PMO system, together with monodispersed gold nanoparticles with diameters comparable to that of the organised pores in the PMO. The role of surface functionalisation in controlling the formation of gold clusters and/or nanoparticles is discussed.
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The synthesis of a styryl functionalised POSS incorporating an encapsulated fluoride ion within a (SiO1.5)8 cage (T8-F) is reported. It was characterised by single crystal XRD, MALDI-MS, FTIR, solution (29Si, 19F, 13C, 1H) and solid state (29Si, 19F) NMR. In the absence of 1H decoupling, the 29Si solution NMR spectrum exhibited a triplet of doublets. In contrast, 1H, 19F and 1H/19F double-decoupling resulted in two, three and one signal, respectively, being consistent with a single Si site whose 29Si NMR signal is modulated by both the proximal aromatic-ring protons and fluoride. The associated SiF coupling constant (2.5 Hz) is substantially lower than expected for a covalent Si-F bond and arises from a fluxional SiF covalent effect in which the F- interacts equivalently with all eight Si atoms. Additional variable temperature NMR studies demonstrated a threshold at -5 °C below which no SiF interactions are observed, and above which an increasing SiF covalent character occurs.
RESUMO
The synthesis of organo-functionalized polyhedral oligomeric silsesquioxanes (POSS, (R-SiO1.5 )n , Tn ) is an area of significant activity. To date, T14 is the largest such cage synthesized and isolated as a single isomer. Herein, we report an unprecedented, single-isomer styryl-functionalized T18 POSS. Unambiguously identified among nine possible isomers by multinuclear solution NMR (1 H, 13 C, and 29 Si), MALDI-MS, FTIR, and computational studies, this is the largest single-isomer functionalized Tn compound isolated to date. A ring-strain model was developed to correlate the 29 Si resonances with the number of 6-, 5-, and/or 4-Si-atom rings that each non-equivalent Si atom is part of. The model successfully predicts the speciation of non-equivalent Si atoms in other families of Tn compounds, demonstrating its general applicability for assigning 29 Si resonances to Si atoms in cage silsesquioxanes and providing a useful tool for predicting Si-atom environments.
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Herein hybrid silica nanoparticles have been engineered to direct the sequential delivery of multiple chemotherapeutic drugs in response to external stimuli such as variations in pH. The nanocarriers consist of conventional MCM-41-type nanoparticles, which have been functionalised with an organic ligand (or stalk) grafted onto the external surface. The stalk is designed to "recognise" a complementary molecule, which serves as a "cap" to block the pores of the nanoparticles. First, camptothecin is introduced into the pores by diffusion prior to capping the pore apertures via molecular recognition. The cap, which is a derivative of 5-fluorouracil, serves as a second cytotoxic drug for synergistic chemotherapy. In vitro tests revealed that negligible release of the drugs occurred at pH 7.4, thus avoiding toxic side effects in the blood stream. In contrast, the stalk/cap complex is destabilised within the endolysosomal compartment (pH 5.5) of cancer cells, where release of the drugs was demonstrated. Furthermore, this environmentally responsive system exhibited a synergistic effect of the two drugs, where the pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo within the pores led to essentially complete elimination of breast cancer cells.
Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Fluoruracila/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/química , Humanos , Células MCF-7 , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
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.
RESUMO
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.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Nanopartículas/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Injeções Intravenosas , Lasers , Microscopia de Fluorescência por Excitação Multifotônica , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/química , Porfirinas/administração & dosagem , Porfirinas/química , Silanos/administração & dosagem , Silanos/química , Nanomedicina Teranóstica/instrumentação , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
Despite the versatility of periodic mesoporous organosilicas (PMOs), the bactericide capacity of these hybrid platforms has seldom been explored. Herein, we describe the synthesis of large-pore phenylene-bridged PMOs, mesostructured by polyion complex (PIC) micelles (PICPMOs) incorporating an antibiotic, neomycin B. A key feature of this approach is that the bioactive molecules are directly encapsulated within the PICPMOs during their formation. The engineered PICPMOs exhibit a well-ordered hexagonal mesophase with a molecular-scale crystallinity and large mesopores (8 nm), which facilitates pH-triggered delivery of the drug. The results obtained with a pathogenic Escherichia coli strain clearly demonstrate the potential of such PICPMOs for antibacterial applications.
RESUMO
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.
RESUMO
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.
RESUMO
Bis(clickable) mesoporous silica nanospheres (ca. 100â 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.
Assuntos
Alcinos/química , Azidas/química , Compostos Azo/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Nanosferas/química , Dióxido de Silício/química , Química Click , Reação de Cicloadição , Doxorrubicina/química , Humanos , Ligantes , PorosidadeRESUMO
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.
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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.
RESUMO
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.
RESUMO
The ever-growing interest for finding efficient and reliable methods for treatment of diseases has set a precedent for the design and synthesis of new functional hybrid materials, namely porous nanoparticles, for controlled drug delivery. Mesoporous silica nanoparticles (MSNPs) represent one of the most promising nanocarriers for drug delivery as they possess interesting chemical and physical properties, thermal and mechanical stabilities, and are biocompatibile. In particular, their easily functionalizable surface allows a large number of property modifications further improving their efficiency in this field. This Concept article deals with the advances on the novel methods of functionalizing MSNPs, inside or outside the pores, as well as within the walls, to produce efficient and smart drug carriers for therapy.
Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Fenômenos Químicos , Humanos , PorosidadeRESUMO
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.
Assuntos
Dissulfetos/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Nanopartículas/metabolismo , Nanopartículas/uso terapêutico , Compostos de Organossilício/síntese química , Compostos de Organossilício/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Células MCF-7 , Estrutura Molecular , Nanopartículas/química , Compostos de Organossilício/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
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.
Assuntos
Nanopartículas/química , Prótons , Dióxido de Silício , Química Click/métodos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Dióxido de Silício/síntese química , Dióxido de Silício/químicaRESUMO
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.
RESUMO
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.
Assuntos
Diagnóstico por Imagem , Ouro , Nanopartículas , Neoplasias/diagnóstico , Neoplasias/terapia , Compostos de Organossilício , Fotoquimioterapia , Fótons , Compostos de Amônio Quaternário , Triazóis , Sobrevivência Celular , Fluorescência , Humanos , Células MCF-7 , Nanopartículas/ultraestrutura , Solubilidade , Espectrometria de FluorescênciaRESUMO
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.