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Stimuli-responsive multifunctional mesoporous silica nanoparticles (MSNs) have been studied intensively during the past decade. A large variety of mesopore capping systems have been designed, initially to show that it could be done and later for biomedical applications such as drug delivery and imaging. On-command release of cargo molecules such as drugs from the pores can be activated by a variety of stimuli. This paper focuses on three noninvasive, biologically usable external stimuli: magnetism, ultrasound, and light. We survey the variety of MSNs that have been and are being used and assess capping designs and the advantages and drawbacks of the nanoplatforms' responses to the various stimuli. We discuss important recent advances, their basic mechanisms, and their requirements for stimulation. On the basis of our survey, we identify fundamental challenges and suggest future directions for research that will unleash the full potential of these fascinating nanosystems for clinical applications.
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Luz , Campos Magnéticos , Nanoestructuras/química , Dióxido de Silicio/química , Nanomedicina Teranóstica , Ondas Ultrasónicas , Portadores de Fármacos/química , Humanos , Nanopartículas Magnéticas de Óxido de Hierro/química , PorosidadRESUMEN
In the presence of an alternating magnetic field (AMF), a superparamagnetic iron oxide nanoparticle (SPION) generates heat. Understanding the local heating mechanism of a SPION in suspension and in a mesoporous silica nanoparticle (MSN) will advance the design of hyperthermia-based nanotheranostics and AMF-stimulated drug delivery in biomedical applications. The AMF-induced heating of single-domain SPION can be explained by the Néel relaxation (reorientation of the magnetization) or the Brownian relaxation (motion of the particle). The latter is investigated using fluorescence depolarization based on detecting the mobility-dependent polarization anisotropy (r) of two luminescence emission bands at different wavelengths corresponded to the europium-doped luminescent SPION (EuSPION) core and the silica-based intrinsically emitting shell of the core-shell MSN. The fluorescence depolarization experiments are carried out with both the free and the silica-encapsulated SPION nanoparticles with and without application of the AMF. The r value of a EuSPION core-mesoporous silica shell in the presence of the AMF does not change, indicating that no additional rotational motion of the core-shell nanoparticles is induced by the AMF, disproving the contribution of Brownian heating and thus supporting Néel relaxation as the dominant heating mechanism.
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Portadores de Fármacos/química , Nanopartículas de Magnetita/química , Dióxido de Silicio/química , Anisotropía , Europio/química , Polarización de Fluorescencia , Colorantes Fluorescentes/química , Calefacción , Porosidad , Rodaminas/químicaRESUMEN
Mesoporous silica nanoparticles (MSNs) are delivery vehicles that can carry cargo molecules and release them on command. The particles used in the applications reported in this Account are around 100 nm in diameter (about the size of a virus) and contain 2.5 nm tubular pores with a total volume of about 1 cm3/g. For the biomedical applications discussed here, the cargo is trapped in the pores until the particles are stimulated to release it. The challenges are to get the particles to the site of a disease and then to deliver the cargo on command. We describe methods to do both, and we illustrate the applicability of the particles to cure cancer and intracellular infectious disease. Our first steps were to design multifunctional nanoparticles with properties that allow them to carry and deliver hydrophobic drugs. Many important pharmaceuticals are hydrophobic and cannot reach the diseased sites by themselves. We describe how we modified MSNs to make them dispersible, imagable, and targetable and discuss in vitro studies. We then present examples of surface modifications that allow them to deliver large molecules such as siRNA. In vivo studies of siRNA delivery to treat triple-negative breast and ovarian cancers are presented. The next steps are to attach nanomachines and other types of caps that trap drug molecules but release them when stimulated. We describe nanomachines that respond autonomously (without human intervention) to stimuli specific to disease sites. A versatile type of machine is a nanovalve that is closed at neutral (blood) pH but opens upon acidification that occurs in endolysosomes of cancer cells. Another type of machine, a snap-top cap, is stimulated by reducing agents such as glutathione in the cytosol of cells. Both of these platforms were studied in vitro to deliver antibiotics to infected macrophages and in vivo to cure and kill the intracellular bacteria M. tuberculosis and F. tularensis. The latter is a tier 1 select agent of bioterrorism. Finally, we describe nanomachines for drug delivery that are controlled by externally administered light and magnetic fields. A futuristic dream for nanotherapy is the ability to control a nano-object everywhere in the body. Magnetic fields penetrate completely and have spatial selectivity governed by the size of the field-producing coil. We describe how to control nanovalves with alternating magnetic fields (AMFs) and superparamagnetic cores inside the MSNs. The AMF heats the cores, and temperature-sensitive caps release the cargo. In vitro studies demonstrate dose control of the therapeutic to cause apoptosis without overheating the cells. Nanocarriers have great promise for therapeutic applications, and MSNs that can carry drugs to the site of a disease to produce a high local concentration without premature release and off-target damage may have the capability of realizing this goal.
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Portadores de Fármacos/química , Nanopartículas/química , Nanotecnología/métodos , Dióxido de Silicio/química , Animales , Antineoplásicos/farmacología , Antituberculosos/farmacología , Liberación de Fármacos , Calefacción , Humanos , Fenómenos Magnéticos , Ratones , ARN Interferente Pequeño/farmacologíaRESUMEN
Magnetic resonance imaging (MRI) is an essential modality for clinical diagnosis, and MRI-guided high-intensity focused ultrasound (MRgHIFU) is a powerful technology for targeted therapy. Clinical applications of MRgHIFU primarily utilize hyperthermia and ablation to treat cancerous tissue, but for drug delivery applications thermal damage is undesirable. A biofriendly MRgHIFU-responsive mesoporous silica nanoparticle (MSN) platform that is stimulated within a physiological safe temperature range has been developed, reducing the possibility of thermal damage to the surrounding healthy tissues. Biocompatible polyethylene glycol (PEG) was employed to cap the pores of MSNs, and the release of cargo molecules by HIFU occurs without substantial temperature increase (â¼4 °C). To visualize by MRI and measure the stimulated delivery in situ, a U.S. Food and Drug Administration (FDA)-approved gadolinium-based contrast agent, gadopentetate dimeglumine (Gd(DTPA)2-), was used as the imageable cargo. Taking advantage of the three-dimensional (3-D) imaging and targeting capabilities of MRgHIFU, the release of Gd(DTPA)2- stimulated by HIFU was pinpointed at the HIFU focal point in 3-D space in a tissue-mimicking gel phantom. The amount of Gd(DTPA)2- released was controlled by HIFU stimulation times and power levels. A positive correlation between the amount of Gd(DTPA)2- released and T1 was found. The MRgHIFU-stimulated cargo release was further imaged in a sample of ex vivo animal tissue. With this technology, the biodistribution of the nanocarriers can be tracked and the MRgHIFU-stimulated cargo release can be pinpointed, opening up an opportunity for future image-guided theranostic applications.
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Medios de Contraste/química , Portadores de Fármacos/química , Gadolinio DTPA/química , Nanopartículas/química , Dióxido de Silicio/química , Animales , Pollos , Medios de Contraste/farmacocinética , Liberación de Fármacos , Gadolinio DTPA/farmacocinética , Imagen por Resonancia Magnética/métodos , Metilcelulosa/química , Leche/química , Fantasmas de Imagen , Polietilenglicoles/química , Prueba de Estudio Conceptual , Sefarosa/química , Nanomedicina Teranóstica/métodos , Factores de Tiempo , Ondas UltrasónicasRESUMEN
Tissue is translucent to shortwave infrared (SWIR) light, rendering optical imaging superior in this region. However, the widespread use of optical SWIR imaging has been limited, in part, by the lack of bright, biocompatible contrast agents that absorb and emit light above 1000 nm. J-Aggregation offers a means to transform stable, near-infrared (NIR) fluorophores into red-shifted SWIR contrast agents. Here we demonstrate that J-aggregates of NIR fluorophore IR-140 can be prepared inside hollow mesoporous silica nanoparticles (HMSNs) to result in nanomaterials that absorb and emit SWIR light. The J-aggregates inside PEGylated HMSNs are stable for multiple weeks in buffer and enable high resolution imaging in vivo with 980 nm excitation.
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Benzotiazoles/química , Medios de Contraste/química , Nanopartículas/química , Dióxido de Silicio/química , Animales , Benzotiazoles/efectos de la radiación , Benzotiazoles/toxicidad , Medios de Contraste/efectos de la radiación , Medios de Contraste/toxicidad , Estabilidad de Medicamentos , Rayos Infrarrojos , Ratones Desnudos , Nanopartículas/toxicidad , Imagen Óptica/métodos , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Dióxido de Silicio/toxicidadRESUMEN
There is significant interest in the development of methods to create hybrid materials that transform capabilities, in particular for Earth-abundant metal oxides, such as TiO2, to give improved or new properties relevant to a broad spectrum of applications. Here we introduce an approach we refer to as 'molecular cross-linking', whereby a hybrid molecular boron oxide material is formed from polyhedral boron-cluster precursors of the type [B12(OH)12]2-. This new approach is enabled by the inherent robustness of the boron-cluster molecular building block, which is compatible with the harsh thermal and oxidizing conditions that are necessary for the synthesis of many metal oxides. In this work, using a battery of experimental techniques and materials simulation, we show how this material can be interfaced successfully with TiO2 and other metal oxides to give boron-rich hybrid materials with intriguing photophysical and electrochemical properties.
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In the version of this Article originally published, Liban M. A. Saleh was incorrectly listed as Liban A. M. Saleh due to a technical error. This has now been amended in all online versions of the Article.
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Triapine (3-AP), is an iron-binding ligand and anticancer drug that is an inhibitor of human ribonucleotide reductase (RNR). Inhibition of RNR by 3-AP results in the depletion of dNTP precursors of DNA, thereby selectively starving fast-replicating cancer cells of nucleotides for survival. The redox-active form of 3-AP directly responsible for inhibition of RNR is the Fe(II)(3-AP)2 complex. In this work, we synthesize 12 analogs of 3-AP, test their inhibition of RNR in vitro, and study the electronic properties of their iron complexes. The reduction and oxidation events of 3-AP iron complexes that are crucial for the inhibition of RNR are modeled with solution studies. We monitor the pH necessary to induce reduction in iron complexes of 3-AP analogs in a reducing environment, as well as the kinetics of oxidation in an oxidizing environment. The oxidation state of the complex is monitored using UV-Vis spectroscopy. Isoquinoline analogs of 3-AP favor the maintenance of the biologically active reduced complex and possess oxidation kinetics that allow redox cycling, consistent with their effective inhibition of RNR seen in our in vitro experiments. In contrast, methylation on the thiosemicarbazone secondary amine moiety of 3-AP produces analogs that form iron complexes with much higher redox potentials, that do not redox cycle, and are inactive against RNR in vitro. The catalytic subunit of human Ribonucleotide Reductase (RNR), contains a tyrosyl radical in the enzyme active site. Fe(II) complexes of 3-AP and its analogs can quench the radical and, subsequently, inactivate RNR. The potency of RNR inhibitors is highly dependent on the redox properties of the iron complexes, which can be tuned by ligand modifications. Complexes are found to be active within a narrow redox window imposed by the cellular environment.
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Antineoplásicos/química , Antineoplásicos/farmacología , Complejos de Coordinación/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Hierro/química , Piridinas/química , Tiosemicarbazonas/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Electroquímica/métodos , Humanos , Estructura Molecular , Oxidación-Reducción/efectos de los fármacos , Ribonucleótido Reductasas/antagonistas & inhibidores , Ribonucleótido Reductasas/metabolismo , Tirosina/químicaRESUMEN
Seedless synthesis of Pd nanorods and their self-assembly into the layered smectic ordering are described. Aqueous Pluronic triblock copolymers (14.3-35.7%) are used as a soft template along with cetyltrimethylammonium bromide for inducing one-dimensional growth of Pd nanorods. Pluronic triblock copolymers are probably the most used polymer surfactants, and they are composed of poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO triblocks. Neither pH adjustment nor AgNO3 and other additives, such as poly(vinyl pyrrolidone) and ethylene glycol, are required to obtain Pd nanorods. Sonochemical synthesis at 43 °C, followed by thermal annealing for 1 h at 65 °C produces Pd nanorods with the aspect ratio from 3.1 (17.9%, Pluronic L-64) to 6.7 (35.7%, Pluronic P-123). Two-dimensional self-assembly of the nanorods is observed, and both nematic ordering between the mesogens and smectic ordering between the layers is identified. Micellar hydrophobic PPO with hydrated PEO coronas are known to self-assemble into many crystalline orders, including cubic, hexagonal, lamellar, and inverse hexagonal mesophases, which extend into cylindrical micelles with increasing temperature. Relatively small size of Pluronic copolymers with regard to general polymers, but rather large size of their micelles and their tendency to organize into crystalline mesophases are thought to contribute to the anisotropic growth of Pd nanorods.
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TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses. We demonstrate TWIST-siRNA (siTWIST) and a novel nanoparticle delivery platform to reverse chemoresistance in an EOC model. Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-HAs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with siTWIST-MSN-HA and cisplatin exhibited specific tumor targeting and reduction of tumor burden. This platform has potential application for overcoming clinical challenges of tumor cell targeting, metastasis and chemoresistance in ovarian and other TWIST overexpressing cancers.
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Cisplatino/uso terapéutico , Ácido Hialurónico/química , Nanopartículas/química , Neoplasias Ováricas/tratamiento farmacológico , ARN Interferente Pequeño/química , Animales , Western Blotting , Línea Celular Tumoral , Femenino , Humanos , Ratones , Microscopía Confocal , Microscopía Fluorescente , Neoplasias Ováricas/metabolismo , ARN Interferente Pequeño/administración & dosificación , Carga Tumoral/efectos de los fármacos , Factores de Transcripción Twist/genética , Factores de Transcripción Twist/metabolismoRESUMEN
We present a synthetic approach to a highly pathogen-selective detection and delivery platform based on the interaction of an antibody nanovalve with a tetrasaccharide from the O-antigen of the lipopolysaccharide (LPS) of Francisella tularensis bacteria, a Tier 1 Select Agent of bioterrorism. Different design considerations are explored, and proof-of-concept for highly pathogen-specific cargo release from mesoporous silica nanoparticles is demonstrated by comparisons of the release of a signal transducer and model drug by LPS from F. tularensis vs Pseudomonas aeruginosa and by F. tularensis live bacteria vs the closely related bacterium Francisella novocida. In addition to the specific response to a biowarfare agent, treatment of infectious diseases in general could benefit tremendously from a delivery platform that releases its antibiotic payload only at the site of infection and only in the presence of the target pathogen, thereby minimizing off-target toxicities.
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Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous silica nanoparticles (MSNs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with cisplatin plus MSN-siTWIST exhibited lower tumor burden than mice treated with cisplatin alone, with most of the effect coming from reduction in disseminated tumors. This platform has potential application for overcoming the clinical challenges of metastasis and chemoresistance in EOC and other TWIST overexpressing cancers.
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Nanopartículas/química , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/terapia , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/uso terapéutico , Tratamiento con ARN de Interferencia/métodos , Dióxido de Silicio/química , Proteína 1 Relacionada con Twist/genética , Animales , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Dendrímeros/química , Femenino , Humanos , Ratones , Ratones Endogámicos NOD , Nanopartículas/ultraestructura , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ovario/metabolismo , Ovario/patología , Porosidad , ARN Interferente Pequeño/genéticaRESUMEN
Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided.
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Sistemas de Liberación de Medicamentos/métodos , Fluoroquinolonas/química , Fluoroquinolonas/uso terapéutico , Nanopartículas/química , Dióxido de Silicio/química , Tularemia/tratamiento farmacológico , Animales , Femenino , Fluoroquinolonas/administración & dosificación , Ratones , Ratones Endogámicos BALB C , MoxifloxacinoRESUMEN
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.
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Alquinos/química , Azidas/química , Compuestos Azo/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Nanosferas/química , Dióxido de Silicio/química , Química Clic , Reacción de Cicloadición , Doxorrubicina/química , Humanos , Ligandos , PorosidadRESUMEN
Despite the worldwide interest generated by periodic mesoporous organosilica (PMO) bulk materials, the design of PMO nanomaterials with controlled morphology remains largely unexplored and their properties unknown. In this work, we describe the first study of PMO nanoparticles (NPs) based on meta-phenylene bridges, and we conducted a comparative structure-property relationship investigation with para-phenylene-bridged PMO NPs. Our findings indicate that the change of the isomer drastically affects the structure, morphology, size, porosity and thermal stability of PMO materials. We observed a much higher porosity and thermal stability of the para-based PMO which was likely due to a higher molecular periodicity. Additionally, the para isomer could generate multipodal NPs at very low stirring speed and upon this discovery we designed a phenylene-ethylene bridged PMO with a controlled Janus morphology. Unprecedentedly high payloads could be obtained from 40 to 110â wt % regardless of the organic bridge of PMOs. Finally, we demonstrate for the first time the co-delivery of two cargos by PMO NPs. Importantly, the cargo stability in PMOs did not require the capping of the pores, unlike pure silica, and the delivery could be autonomously triggered in cancer cells by acidic pH with nearly 70 % cell killing.
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Antineoplásicos/química , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Nanoestructuras/química , Compuestos de Organosilicio/química , Nanopartículas/uso terapéutico , Porosidad , Propiedades de SuperficieRESUMEN
We describe biodegradable mesoporous hybrid nanoparticles (NPs) in the presence of proteins and their applications for drug delivery. We synthesized oxamide phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of a silica source which had remarkably high organic content and high surface areas. Oxamide functions provided biodegradability in the presence of trypsin model proteins. MON displayed exceptionally high payloads of hydrophilic and hydrophobic drugs (up to 84â wt %), and a unique zero premature leakage without the pore capping, unlike mesoporous silica. MON were biocompatible and internalized into cancer cells for drug delivery.
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Nanopartículas/química , Compuestos de Organosilicio/química , Ácido Oxámico/análogos & derivados , Dióxido de Silicio/química , Sistemas de Liberación de Medicamentos , Interacciones Hidrofóbicas e Hidrofílicas , Ácido Oxámico/químicaRESUMEN
Many machines (including nanomachines) consist of a solid support with moving parts that can undergo large amplitude motion to carry out specific tasks. In this Minireview, we will describe nanomachines that are supported on mesoporous silica nanoparticles that are typically 50-100 nanometers in diameter and have an array of open, readily accessible pores with an average width of a few nanometers. For triggering a large amplitude motion of the moving parts, we will focus primarily on external stimuli such as heat or light. As for the specific task the machines are carrying out, this Minireview will focus on the controlled release of pharmaceutically active agents in biomedical applications. We will discuss examples of how nanomachines can be used for remotely controlled cargo release and how existing machines that were originally designed to respond to internal physiological stimuli could be reconfigured to respond to external stimuli instead.
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Investigación Biomédica , Nanopartículas/química , Nanotecnología , Dióxido de Silicio/química , PorosidadRESUMEN
Creation of structural complexity by simple experimental control will be an attractive approach for the preparation of nanomaterials, as a classical bottom-up method is supplemented by a more efficient and more direct artificial engineering method. In this study, structural manipulation of MCM-41 type mesoporous silica is investigated by generating and imbedding hard magnetic CoFe2O4 nanoparticles into mesoporous silica. Depending on the heating rate and target temperature, mesoporous silica undergoes a transformation in shape to form hollow silica, framed silica with interior voids, or melted silica with intact mesostructures. Magnetism is governed by the major CoFe2O4 phase, and it is affected by antiferromagnetic hematite (α-Fe2O3) and olivine-type cobalt silicate (Co2SiO4), as seen in its paramagnetic behavior at the annealing temperature of 430 °C. The early formation of Co2SiO4 than what is usually observed implies the effect of the partial substitution of Fe in the sites of Co. Under slow heating (2.5 °C min(-1)) mesostructures are preserved, but with significantly smaller mesopores (d100 = 1.5 nm). In addition, nonstoichiometric CoxFe1-xO with metal vacancies at 600 °C, and spinel Co3O4 at 700 °C accompany major CoFe2O4. The amorphous nature of silica matrix is thought to contribute significantly to these structurally diverse and rich phases, enabled by off-stoichiometry between Si and O, and accelerated by the diffusion of metal cations into SiO4 polyhedra at an elevated temperature.
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A facile, reproducible, and scalable method was explored to construct uniform Au@poly(acrylic acid) (PAA) Janus nanoparticles (JNPs). The as-prepared JNPs were used as templates to preferentially grow a mesoporous silica (mSiO2 ) shell and Au branches separately modified with methoxy-poly(ethylene glycol)-thiol (PEG) to improve their stability, and lactobionic acid (LA) for tumor-specific targeting. The obtained octopus-type PEG-Au-PAA/mSiO2 -LA Janus NPs (PEG-OJNP-LA) possess pH and NIR dual-responsive release properties. Moreover, DOX-loaded PEG-OJNP-LA, upon 808â nm NIR light irradiation, exhibit obviously higher toxicity at the cellular and animal levels compared with chemotherapy or photothermal therapy alone, indicating the PEG-OJNP-LA could be utilized as a multifunctional nanoplatform for inâ vitro and inâ vivo actively-targeted and chemo-photothermal cancer therapy.
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Nanopartículas/química , Neoplasias Experimentales/tratamiento farmacológico , Compuestos Orgánicos de Oro/farmacología , Temperatura , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Disacáridos/química , Disacáridos/farmacología , Células HeLa , Células Hep G2 , Humanos , Rayos Infrarrojos , Rayos Láser , Ratones , Ratones Endogámicos , Neoplasias Experimentales/patología , Compuestos Orgánicos de Oro/síntesis química , Compuestos Orgánicos de Oro/química , Fototerapia , Polietilenglicoles/química , Polietilenglicoles/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Relación Estructura-ActividadRESUMEN
Nanoimpellers are mesoporous silica nanoparticles that contain azobenzene derivatives bonded inside the pores and rely on the continuous photoisomerization of multiple azobenzenes to release cargo under near UV irradiation. A recent study employs upconversion nanocrystal embedded particles to replace UV light with IR light to stimulate nanoimpellers. However, the photothermal effect of IR irradiation and its likely contribution to the observed release behavior are not examined. It is found that, in the absence of upconversion nanocrystals, the azobenzene co-condensed silica particles still respond to 980 nm illumination, which increases the nanoparticle temperature by 25 °C in 15 min, experimentally measured by an encapsulated nanothermometer. After suppressing the heating, the IR irradiation does not initiate the release, indicating that optical heating, not upconverted light, is responsible for the triggered cargo release. The results are explained by numerical analyses.