RESUMO
Hydrated uranyl fluoride, [(UO2F2)(H2O)]7·4H2O, is not stable at elevated water vapor pressure, undergoing a complete loss of fluorine to form a uranyl hydroxide hydrate. Powder X-ray diffraction data of the resultant uranyl hydroxide species is presented for the first time, along with Raman and infrared (IR) spectra. The new uranyl hydroxide species is structurally similar to the layered uranyl hydroxide hydrate minerals schoepite and metaschoepite, but has a significantly expanded interlayer spacing (c = 15.12 vs. 14.73 Å), suggesting that additional H2O molecules may be present between the uranyl layers. Comparison of the Raman and IR spectra of this new uranyl hydroxide hydrate and synthetic metaschoepite ([(UO2)4O(OH)6]·5H2O) suggests that the equatorial environment of the uranyl ion may differ and that H2O molecules in the new species participate in stronger hydrogen bonds. In addition, the interlayer spacing of both this new uranyl hydroxide species and synthetic metaschoepite is shown to be sensitive to the environmental humidity, contracting and re-expanding with desiccation and rehydration. Structural distinction between the new uranyl hydroxide species and synthetic metaschoepite is confirmed by a comparison of the thermal behavior; unlike metaschoepite, the new hydrate does not form α-UO2(OH)2 upon dehydration.
RESUMO
We have demonstrated the solid-state formation of a uranyl peroxide (UP) species from hydrated uranyl fluoride via a uranyl hydroxide intermediate, the first observation of a UP species formed in a solid-state reaction. Water vapor pressure is shown to be a driving factor of both the loss of fluorine and the subsequent formation of peroxo units. We have ruled out a photochemical mechanism for formation of the UP species by demonstrating that the same reaction occurs in the dark. A radiolytic mechanism is unlikely because of the low radioactivity of the sample material, suggesting the existence of a novel UP formation mechanism.
RESUMO
Gating of mesoporous silica nanoparticles (MSNs) with the stimuli-responsive poly(ß-amino ester) has been achieved. This hybrid nanocarrier releases doxorubicin (DOX) under acidic conditions or in the presence of porcine liver esterase. The DOX loaded poly(ß-amino ester)-capped MSNs reduce cell viability when tested on MDA-MB-231 human breast cancer cells.
Assuntos
Portadores de Fármacos/química , Esterases/metabolismo , Nanopartículas/química , Polímeros/química , Dióxido de Silício/química , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/toxicidade , Esterases/química , Humanos , Concentração de Íons de Hidrogênio , Porosidade , SuínosRESUMO
A sugar and pH dual-responsive controlled release system, which is highly specific towards molecular stimuli, has been developed based on the binding between catechol and boronic acid on a platform of mesoporous silica nanoparticles (MSNs). By grafting phenylboronic acid stalks onto the silica surface, catechol-containing ß-cyclodextrins can be attached to the orifices of the MSNs' nanopores through formation of boronate esters which block access to the nanopores. These esters are stable enough to prevent cargo molecules from escaping. The boronate esters disassociate in the presence of sugars, enabling the molecule-specific controlled-release feature of this hybrid system. The rate of release has been found to be tunable by varying both the structures and the concentrations of sugars, as a result of the competitive binding nature associated with the mechanism of its operation. Acidification also induces the release of cargo molecules. Further investigations show that the presence of both a low pH and sugar molecules provides cooperative effects which together control the rate of release.
Assuntos
Carboidratos/química , Preparações de Ação Retardada/química , Concentração de Íons de Hidrogênio , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Nanoporos/ultraestrutura , Cristalização/métodos , Preparações de Ação Retardada/administração & dosagem , Difusão , Teste de Materiais , Nanocápsulas/administração & dosagem , Tamanho da Partícula , PorosidadeRESUMO
Two azobenzene α-cyclodextrin based nanovalves are designed, synthesized and assembled on mesoporous silica nanoparticles. Under aqueous conditions, the cyclodextrin cap is tightly bound to the azobenzene moiety and capable of holding back loaded cargo molecules. Upon irradiation with a near-UV light laser, trans to cis-photoisomerization of azobenzene initiates a dethreading process, which causes the cyclodextrin cap to unbind followed by the release of cargo. The addition of a bulky stopper to the end of the stalk allows this design to be reversible; complete dethreading of cyclodextrin as a result of unbinding with azobenzene is prevented as a consequence of steric interference. As a result, thermal relaxation of cis- to trans-azobenzene allows for the rebinding of cyclodextrin and resealing of the nanopores, a process which entraps the remaining cargo. Two stalks were designed with different lengths and tested with alizarin red S and propidium iodide. No cargo release was observed prior to light irradiation, and the system was capable of multiuse. On/off control was also demonstrated by monitoring the release of cargo when the light stimulus was applied and removed, respectively.
RESUMO
The incorporation of silica nanoparticles into drug delivery vehicles, and other nanotech platforms, has experienced rapid and significant growth over the past decade. However, as these nanoparticle-based systems become more and more complex, the methods used to analyze these systems have evolved at a comparatively much slower pace, resulting in the need for researchers to expand their toolbox and devise new strategies to characterize these materials. This article describes how X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were recently employed in the analysis of two separate drug delivery systems which contain organic compounds covalently attached to the surfaces of silica nanoparticles. These techniques provided a deluge of qualitative and quantitative information about these drug delivery systems, and have several clear advantages over more common characterization procedures such as Fourier transform infrared spectroscopy (FT-IR) and solid state nuclear magnetic resonance (SSNMR). Thus, XPS and ToF-SIMS should be an integral component of the standard characterization protocol for any nanoparticle-based assemblies-particularly silica-based drug delivery systems-as this field of research continues to develop.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Espectrometria de Massas , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions.
Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/química , Compostos Organometálicos/administração & dosagem , Paclitaxel/administração & dosagem , Dióxido de Silício/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Luz , Modelos Moleculares , Compostos Organometálicos/farmacologia , Paclitaxel/farmacologiaAssuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Dióxido de Silício/química , beta-Ciclodextrinas/farmacologia , Benzimidazóis , Ácidos Cumáricos/metabolismo , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Tamanho da Partícula , Porosidade , Propionatos , EstereoisomerismoRESUMO
Medicine can benefit significantly from advances in nanotechnology because nanoscale assemblies promise to improve on previously established therapeutic and diagnostic regimes. Over the past decade, the use of delivery platforms has attracted attention as researchers shift their focus toward new ways to deliver therapeutic and/or diagnostic agents and away from the development of new drug candidates. Metaphorically, the use of delivery platforms in medicine can be viewed as the "bow-and-arrow" approach, where the drugs are the arrows and the delivery vehicles are the bows. Even if one possesses the best arrows that money can buy, they will not be useful if one does not have the appropriate bow to deliver the arrows to their intended location. Currently, many strategies exist for the delivery of bioactive agents within living tissue. Polymers, dendrimers, micelles, vesicles, and nanoparticles have all been investigated for their use as possible delivery vehicles. With the growth of nanomedicine, one can envisage the possibility of fabricating a theranostic vector that could release powerful therapeutics and diagnostic markers simultaneously and selectively to diseased tissue. In our design of more robust theranostic delivery systems, we have focused our attention on using mesoporous silica nanoparticles (SNPs). The payload "cargo" molecules can be stored within this robust domain, which is stable to a wide range of chemical conditions. This stability allows SNPs to be functionalized with stimulus-responsive mechanically interlocked molecules (MIMs) in the shape of bistable rotaxanes and psuedorotaxanes to yield mechanized silica nanoparticles (MSNPs). In this Account, we chronicle the evolution of various MSNPs, which came about as a result of our decade-long collaboration, and discuss advances in the synthesis of novel hybrid SNPs and the various MIMs which have been attached to their surfaces. These MIMs can be designed in such a way that they either change shape or shed off some of their parts in response to a specific stimulus, such as changes in redox potential, alterations in pH, irradiation with light, or the application of an oscillating magnetic field, allowing a theranostic payload to be released from the nanopores to a precise location at the appropiate time. We have also shown that these integrated systems can operate not only within cells, but also in live animals in response to pre-existing biological triggers. Recognizing that the theranostics of the future could offer a fresh approach to the treatment of degenerative diseases including cancer, we aim to start moving out of the chemical domain and into the biological one. Some MSNPs are already being tested in biological systems.
Assuntos
Fenômenos Mecânicos , Nanomedicina/métodos , Nanopartículas/uso terapêutico , Dióxido de Silício/química , Animais , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapêutico , Humanos , Nanopartículas/química , Água/químicaRESUMO
An approach to the design and fabrication of mechanized mesoporous silica nanoparticles is demonstrated at the proof of principle level. It relies on the reductive cleavage of disulfide bonds within an integrated nanosystem, wherein surface-bound rotaxanes incorporate disulfide bonds in their stalks, which are encircled by cucurbit[6]uril or alpha-cyclodextrin rings, until reductive chemistry is performed, resulting in the snapping of the stalks of the rotaxanes, leading to cargo release from the inside of the nanoparticles.
Assuntos
Nanopartículas/química , Dióxido de Silício/química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Estrutura Molecular , Oxirredução , Rodaminas/química , alfa-Ciclodextrinas/químicaRESUMO
Time and time again humanity is faced with a unifying global crisis that crosses the many great divides in different societies and serves to bring once segregated communities back together as a collective whole. This global community instinctively turns to science to develop the means of addressing its most pressing problems. More often than not, these forces dictate the direction that scientific research takes. This influence is no more apparent than in the field of supramolecular chemistry where, for decades now, its responsibility to tackle such issues has been put on the back burner as a consequence of a lack of platforms with which to deliver this contemporary brand of chemistry to meaningful applications. However, the tide is slowly turning as new materials emerge from the field of nanotechnology that are poised to host the many attractive attributes that are inherent in the chemistry of these supermolecules and also in the mechanostereochemistry of mechanically interlocked molecules (MIMs), which can be reused as a sequel to supramolecular chemistry. Mesoporous silica nanoparticles (SNPs) have proven to be supremely effective solid supports as their surfaces are easily functionalised with either supermolecules or MIMs. In turn, the blending of supramolecular chemistry and mechanostereochemistry with mesoporous SNPs has led to a new class of materials - namely, mechanised SNPs that are effectively biological nanoscale 'bombs' that have the potential to infiltrate cells and then, upon the pulling of a chemical trigger, explode! The development of these materials has been driven by the need to devise new therapies for the treatment of cancer. Recent progress in research promises not only to control the acuteness of this widespread and insidious disease, but also to make the harsh treatment less debilitating to patients. This global scourge is the unifying force that has brought together supramolecular chemistry, mechanostereochemistry and nanotechnology, uniting these three communities for the common good. At the nanoscale level, the mechanism for the release of cargos from the confines of the nanopores in the SNPs is accomplished by way of mechanical modifications made on the surface of these functionalised supports. These mechanical motions rely on both supramolecular, i.e., host-guest complexes, and mechanostereochemical phenomena (e.g., bistable rotaxanes), which are often stimulated by changes in pH, light and redox potentials, in addition to enzymatic catalysis. The future of this field lies in the development of 'smart bombs' wherein the loaded mechanised SNPs are endocytosed selectively by cancer cells, whereupon an intracellular trigger causes release of a cytotoxin, effectively leading to apoptosis. This review serves to highlight (1) the evolution of surface-functionalisation of SNPs with supermolecules and also with MIMs, (2) the mechanisms through which controlled-release of cargo from mechanised SNPs occurs, and (3) results from the in vitro application of these mechanised SNPs.