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Because of their large surface areas, nanotubes and nanowires demonstrate exquisite mechanical coupling to their surroundings, promising advanced sensors and nanomechanical devices. However, this environmental sensitivity has resulted in several ambiguous observations of vibrational coupling across various experiments. Herein, we demonstrate a temperature-dependent Radial Breathing Mode (RBM) frequency in free-standing, electron-diffraction-assigned Double-Walled Carbon Nanotubes (DWNTs) that shows an unexpected and thermally reversible frequency downshift of 10 to 15%, for systems isolated in vacuum. An analysis based on a harmonic oscillator model assigns the distinctive frequency cusp, produced over 93 scans of 3 distinct DWNTs, along with the hyperbolic trajectory, to a reversible increase in damping from graphitic ribbons on the exterior surface. Strain-dependent coupling from self-tensioned, suspended DWNTs maintains the ratio of spring-to-damping frequencies, producing a stable saturation of RBM in the low-tension limit. In contrast, when the interior of DWNTs is subjected to a water-filling process, the RBM thermal trajectory is altered to that of a Langmuir isobar and elliptical trajectories, allowing measurement of the enthalpy of confined fluid phase change. These mechanisms and quantitative theory provide new insights into the environmental coupling of nanomechanical systems and the implications for devices and nanofluidic conduits.
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Nanofluidic channels impose extreme confinement on water and ions, giving rise to unusual transport phenomena strongly dependent on the interactions at the channel-wall interface. Yet how the electronic properties of the nanofluidic channels influence transport efficiency remains largely unexplored. Here we measure transport through the inner pores of sub-1 nm metallic and semiconducting carbon nanotube porins. We find that water and proton transport are enhanced in metallic nanotubes over semiconducting nanotubes, whereas ion transport is largely insensitive to the nanotube bandgap value. Molecular simulations using polarizable force fields highlight the contributions of the anisotropic polarizability tensor of the carbon nanotubes to the ion-nanotube interactions and the water friction coefficient. We also describe the origin of the proton transport enhancement in metallic nanotubes using deep neural network molecular dynamics simulations. These results emphasize the complex role of the electronic properties of nanofluidic channels in modulating transport under extreme nanoscale confinement.
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PURPOSE: A comparative assessment was performed to evaluate the potential of particle sizing by an ensemble based conventional dynamic light scattering (DLS) technique and an emerging technology based on tunable resistive pulse sensing (TRPS) using particle by particle approach by evaluating three different types of vaccine formulations representing three case studies and showing the limitation of each technique, instrument variability, sensitivity, and the resolution in mixed population. METHODS: Three types of in-house vaccine formulations- a protein antigen, an outer membrane vesicle and viral particles were simultaneously evaluated by TRPS based Exoid and two DLS instruments-Zetatrac and Zetasizer for particle size distribution, aggregates, and resolution of polydisperse species. RESULTS: The data from first case study show the risk of possible size overestimation and size averaging in polydisperse samples in DLS measurements which can be addressed by the TRPS analysis. It also shows how TRPS may be utilized only to large size antigens due to its limited size range. The second case study highlights the difference in the sensitivities of two DLS instruments working on the same principle. The third case study show that how TRPS can better resolve the large aggregate species compare to DLS in polydisperse samples. CONCLUSION: This analysis shows that TRPS can be used as an orthogonal technique in addition to conventional DLS based methods for more precise and in-depth characterization. Both techniques are efficient in size characterization and produce comparable results, however the choice will depend on the type of formulation and size range to be evaluated.
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Difusão Dinâmica da Luz , Tamanho da Partícula , Vacinas , Difusão Dinâmica da Luz/métodos , Vacinas/química , Composição de Medicamentos/métodosRESUMO
Understanding the behavior of water contacting two-dimensional materials, such as hexagonal boron nitride (hBN), is important in practical applications, including seawater desalination and energy harvesting. Water, being a polar solvent, can strongly polarize the hBN surface via the electric fields that it generates. However, there is a lack of molecular-level understanding about the role of polarization effects at the hBN/water interface, including its effect on the wetting properties of water. In this study, we develop a theoretical framework that introduces an all-atomistic polarizable force field to accurately model the interactions of water molecules with hBN surfaces. The force field is then utilized to self-consistently describe the water-induced polarization of hBN using the classical Drude oscillator model, including predicting the hBN-water binding energies which are found to be in excellent agreement with diffusion Monte Carlo (DMC) predictions. By carrying out molecular dynamics (MD) simulations, we demonstrate that the polarizable force field yields a water contact angle on multilayered hBN which is in close agreement with the recent experimentally reported values. Conversely, an implicit modeling of the hBN-water polarization energy utilizing a Lennard-Jones (LJ) potential, a commonly utilized approximation in previous MD simulation studies, leads to a considerably lower water contact angle. This difference in the predicted contact angles is attributed to the significant energy-entropy compensation resulting from the incorporation of polarization effects at the hBN-water interface. Our work highlights the importance of self-consistently modeling the hBN-water polarization energy and offers insights into the wetting-related interfacial phenomena of water on polarizable materials.
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Rare but consistent reports of abscopal remission in patients challenge the notion that radiotherapy (RT) is a local treatment; radiation-induced cancer cell death can trigger activation and recruitment of dendritic cells to the primary tumor site, which subsequently initiates systemic immune responses against metastatic lesions. Although this abscopal effect was initially considered an anomaly, combining RT with immune checkpoint inhibitor therapies has been shown to greatly improve the incidence of abscopal responses via modulation of the immunosuppressive tumor microenvironment. Preclinical studies have demonstrated that nanomaterials can further improve the reliability and potency of the abscopal effect for various different types of cancer by (1) altering the cell death process to be more immunogenic, (2) facilitating the capture and transfer of tumor antigens from the site of cancer cell death to antigen-presenting cells, and (3) co-delivering immune checkpoint inhibitors along with radio-enhancing agents. Several unanswered questions remain concerning the exact mechanisms of action for nanomaterial-enhanced RT and for its combination with immune checkpoint inhibition and other immunostimulatory treatments in clinically relevant settings. The purpose of this article is to summarize key recent developments in this field and also highlight knowledge gaps that exist in this field. An improved mechanistic understanding will be critical for clinical translation of nanomaterials for advanced radio-immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Nanoestruturas , Neoplasias , Humanos , Reprodutibilidade dos Testes , Imunoterapia , Neoplasias/radioterapia , Nanotecnologia , Nanoestruturas/uso terapêutico , Microambiente TumoralRESUMO
Surfactants are widely used to disperse single-walled carbon nanotubes (SWCNTs) and other nanomaterials for liquid-phase processing and characterization. Traditional techniques, however, demand high surfactant concentrations, often in the range of 1-2 wt/v% of the solution. Here, we show that optimal dispersion efficiency can be attained at substantially lower surfactant concentrations of approximately 0.08 wt/v%, near the critical micelle concentration. This unexpected observation is achieved by introducing "bare" nanotubes into water containing the anionic surfactant sodium deoxycholate (DOC) through a superacid-surfactant exchange process that eliminates the need for ultrasonication. Among the diverse ionic surfactants and charged biopolymers explored, DOC exhibits the highest dispersion efficiency, outperforming sodium cholate, a structurally similar bile salt surfactant containing just one additional oxygen atom compared to DOC. Employing all-atomistic molecular dynamics simulations, we unravel that the greater stabilization by DOC arises from its higher binding affinity to nanotubes and a substantially larger free energy barrier that resists nanotube rebundling. Further, we find that this barrier is nonelectrostatic in nature and does not obey the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal stability, underscoring the important role of nonelectrostatic dispersion and hydration interactions at the nanoscale, even in the case of ionic surfactants like DOC. These molecular insights advance our understanding of surfactant chemistry at the bare nanotube limit and suggest low-energy, surfactant-efficient solution processing of SWCNTs and potentially other nanomaterials.
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Confined fluids and electrolyte solutions in nanopores exhibit rich and surprising physics and chemistry that impact the mass transport and energy efficiency in many important natural systems and industrial applications. Existing theories often fail to predict the exotic effects observed in the narrowest of such pores, called single-digit nanopores (SDNs), which have diameters or conduit widths of less than 10 nm, and have only recently become accessible for experimental measurements. What SDNs reveal has been surprising, including a rapidly increasing number of examples such as extraordinarily fast water transport, distorted fluid-phase boundaries, strong ion-correlation and quantum effects, and dielectric anomalies that are not observed in larger pores. Exploiting these effects presents myriad opportunities in both basic and applied research that stand to impact a host of new technologies at the water-energy nexus, from new membranes for precise separations and water purification to new gas permeable materials for water electrolyzers and energy-storage devices. SDNs also present unique opportunities to achieve ultrasensitive and selective chemical sensing at the single-ion and single-molecule limit. In this review article, we summarize the progress on nanofluidics of SDNs, with a focus on the confinement effects that arise in these extremely narrow nanopores. The recent development of precision model systems, transformative experimental tools, and multiscale theories that have played enabling roles in advancing this frontier are reviewed. We also identify new knowledge gaps in our understanding of nanofluidic transport and provide an outlook for the future challenges and opportunities at this rapidly advancing frontier.
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Recent measurements of fluids under extreme confinement, including water within narrow carbon nanotubes, exhibit marked deviations from continuum theoretical descriptions. In this work, we generate precise carbon nanotube replicates that are filled with water, closed from external mass transfer, and studied over a wide temperature range by Raman spectroscopy. We study segments that are empty, partially filled, and completely filled with condensed water from -80 to 120 °C. Partially filled, nanodroplet states contain submicron vapor-like and liquid-like domains and are analyzed using a Clausius-Clapeyron-type model, yielding heats of condensation of water inside closed 1.32 nm diameter carbon nanotubes (3.32 ± 0.10 kJ/mol and 3.72 ± 0.11 kJ/mol) and 1.45 nm diameter carbon nanotubes (3.50 ± 0.07 kJ/mol) that are lower than the bulk enthalpy of vaporization and closer to the bulk enthalpy of fusion. Favored partial filling fractions are calculated, highlighting the effect of subnanometer changes in confining diameter on fluid properties and suggesting the promise of molecular engineering of nanoconfined liquid/vapor interfaces for water treatment or membrane distillation.
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For over 100 years, the Nernst-Einstein relation has linked a charged particle's electrophoretic mobility and diffusion coefficient. Here we report experimental measurements of diffusion and electromigration of K+ ions in narrow 0.8-nm-diameter single-walled carbon nanotube porins (CNTPs) and demonstrate that the Nernst-Einstein relation in these channels breaks down by more than three orders of magnitude. Molecular dynamics simulations using polarizable force fields show that K+ ion diffusion in CNTPs in the presence of a single-file water chain is three orders of magnitude slower than bulk diffusion. Intriguingly, the simulations also reveal a disintegration of the water chain upon application of electric fields, resulting in the formation of distinct K+-water clusters, which then traverse the CNTP at high velocity. Finally, we show that although individual ion-water clusters still obey the Nernst-Einstein relation, the overall relation breaks down because of two distinct mechanisms for ion diffusion and electromigration.
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Porous graphene and other atomically thin 2D materials are regarded as highly promising membrane materials for high-performance gas separations due to their atomic thickness, large-scale synthesizability, excellent mechanical strength, and chemical stability. When these atomically thin materials contain a high areal density of gas-sieving nanoscale pores, they can exhibit both high gas permeances and high selectivities, which is beneficial for reducing the cost of gas-separation processes. Here, recent modeling and experimental advances in nanoporous atomically thin membranes for gas separations is discussed. The major challenges involved, including controlling pore size distributions, scaling up the membrane area, and matching theory with experimental results, are also highlighted. Finally, important future directions are proposed for real gas-separation applications of nanoporous atomically thin membranes.
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The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
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Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Coronavirus/metabolismo , Desenvolvimento de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Benzamidas/farmacologia , Linhagem Celular , Simulação por Computador , Coronavirus/química , Bases de Dados de Produtos Farmacêuticos , Descoberta de Drogas/métodos , Interações Hospedeiro-Patógeno , Humanos , Imidazóis/farmacologia , Quinases Associadas a Receptores de Interleucina-1/metabolismo , SARS-CoV-2/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Triazinas/farmacologia , Tratamento Farmacológico da COVID-19RESUMO
The development of nanoporous single-layer graphene membranes for gas separation has prompted increasing theoretical investigations of gas transport through graphene nanopores. However, computer simulations and theories that predict gas permeances through individual graphene nanopores are not suitable to describe experimental results, because a realistic graphene membrane contains a large number of nanopores of diverse sizes and shapes. With this need in mind, here, we generate nanopore ensembles in silico by etching carbon atoms away from pristine graphene with different etching times, using a kinetic Monte Carlo algorithm developed by our group for the isomer cataloging problem of graphene nanopores. The permeances of H2, CO2, and CH4 through each nanopore in the ensembles are predicted using transition state theory based on classical all-atomistic force fields. Our findings show that the total gas permeance through a nanopore ensemble is dominated by a small fraction of large nanopores with low energy barriers of pore crossing. We also quantitatively predict the increase of the gas permeances and the decrease of the selectivities between the gases as functions of the etching time of graphene. Furthermore, by fitting the theoretically predicted selectivities to the experimental ones reported in the literature, we show that nanopores in graphene effectively expand as the temperature of permeation measurement increases. We propose that this nanopore "expansion" is due to the desorption of contaminants that partially clog the graphene nanopores. In general, our study highlights the effects of the pore size and shape distributions of a graphene nanopore ensemble on its gas separation properties and calls into attention the potential effect of pore-clogging contamination in experiments.
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Solid/water interfaces, in which salt ions come in close proximity to solids, are ubiquitous in nature. Because water is a polar solvent and salt ions are charged, a long-standing puzzle involving solid/water interfaces is how do the electric fields exerted by the salt ions and the interfacial water molecules polarize the charge distribution in the solid and how does this polarization, in turn, influence ion adsorption at any solid/water interface. Here, using state-of-the-art polarizable force fields derived from quantum chemical simulations, we perform all-atomistic molecular dynamics simulations to investigate the adsorption of various ions comprising the well-known Hofmeister series at the graphene/water interface, including comparing with available experimental data. Our findings reveal that, in vacuum, the ionic electric field-induced polarization of graphene results in a significantly large graphene-ion polarization energy, which drives all salt ions to adsorb to graphene. On the contrary, in the presence of water molecules, we show that the ions and the water molecules exert waves of molecular electric fields on graphene which destructively interfere with each other. This remarkable phenomenon is shown to cause a water-mediated screening of more than 85% of the graphene-ion polarization energy. Finally, by investigating superhydrophilic and superhydrophobic model surfaces, we demonstrate that this phenomenon occurs universally at all solid/water interfaces and results in a significant weakening of the ion-solid interactions, such that ion specific effects are governed primarily by a competition between the ion-water and water-water interactions, irrespective of the nature of the solid/water interface.
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Although the structure and properties of water under conditions of extreme confinement are fundamentally important for a variety of applications, they remain poorly understood, especially for dimensions less than 2 nm. This problem is confounded by the difficulty in controlling surface roughness and dimensionality in fabricated nanochannels, contributing to a dearth of experimental platforms capable of carrying out the necessary precision measurements. In this work, we utilize an experimental platform based on the interior of lithographically segmented, isolated single-walled carbon nanotubes to study water under extreme nanoscale confinement. This platform generates multiple copies of nanotubes with identical chirality, of diameters from 0.8 to 2.5 nm and lengths spanning 6 to 160 µm, that can be studied individually in real time before and after opening, exposure to water, and subsequent water filling. We demonstrate that, under controlled conditions, the diameter-dependent blue shift of the Raman radial breathing mode (RBM) between 1 and 8 cm-1 measures an increase in the interior mechanical modulus associated with liquid water filling, with no response from exterior water exposure. The observed RBM shift with filling demonstrates a non-monotonic trend with diameter, supporting the assignment of a minimum of 1.81 ± 0.09 cm-1 at 0.93 ± 0.08 nm with a nearly linear increase at larger diameters. We find that a simple hard-sphere model of water in the confined nanotube interior describes key features of the diameter-dependent modulus change of the carbon nanotube and supports previous observations in the literature. Longer segments of 160 µm show partial filling from their ends, consistent with pore clogging. These devices provide an opportunity to study fluid behavior under extreme confinement with high precision and repeatability.
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Nanoporous graphene is a promising candidate material for gas separation membranes, due to its atomic thickness and low cross-membrane transport resistance. The mechanisms of gas permeation through graphene nanopores, in both the large and small pore size limits, have been reported in the literature. However, mechanistic insights into the crossover from the small pore size limit to the large pore size limit are still lacking. In this study, we develop a comprehensive theoretical framework to predict gas permeance through graphene nanopores having a wide range of diameters using analytical equations. We formulate the transport kinetics associated with the direct impingement from the bulk and with the surface diffusion from the adsorption layer on graphene and then combine them to predict the overall gas permeation rate using a reaction network model. We also utilize molecular dynamics simulations to validate and calibrate our theoretical model. We show that the rates of both the direct impingement and the surface diffusion pathways need to be corrected using different multiplicative factors, which are functions of temperature, gas kinetic diameter, and pore diameter. Further, we find a minor spillover pathway that originates from the surface adsorption layer, but is not included in our theoretical model. Finally, we utilize the corrected model to predict the permeances of CO2, CH4, and Ar through graphene nanopores. We show that as the pore diameter increases, gas transport through graphene nanopores can transition from being translocation dominated (pore diameter < 0.7 nm), to surface pathway dominated (pore diameter 1-2 nm), and finally to direct pathway dominated (pore diameter > 4 nm). The various gas permeation mechanisms outlined in this study will be particularly useful for the rational design of membranes made out of two-dimensional materials such as graphene for gas separation applications.
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Aqueous electrolyte solutions containing multivalent ions exhibit various intriguing properties, including attraction between like-charged colloidal particles, which results from strong ion-ion correlations. In contrast, the classical Derjaguin-Landau-Verwey-Overbeek theory of colloidal stability, based on the Poisson-Boltzmann mean-field theory, always predicts a repulsive electrostatic contribution to the disjoining pressure. Here, we formulate a general theory of surface forces, which predicts that the contribution to the disjoining pressure resulting from ion-ion correlations is always attractive and can readily dominate over entropic-induced repulsions for solutions containing multivalent ions, leading to the phenomenon of like-charge attraction. Ion-specific short-range hydration interactions, as well as surface charge regulation, are shown to play an important role at smaller separation distances but do not fundamentally change these trends. The theory is able to predict the experimentally observed strong cohesive forces reported in cement pastes, which result from strong ion-ion correlations involving the divalent calcium ion.
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The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1â¯month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1â¯month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.
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Antineoplásicos Fitogênicos/administração & dosagem , Compostos de Cálcio/administração & dosagem , Sistemas de Liberação de Medicamentos , Substâncias Luminescentes/administração & dosagem , Nanopartículas/administração & dosagem , Paclitaxel/administração & dosagem , Polietilenoglicóis/administração & dosagem , Compostos de Tungstênio/administração & dosagem , Animais , Antineoplásicos Fitogênicos/química , Compostos de Cálcio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimiorradioterapia , Liberação Controlada de Fármacos , Feminino , Humanos , Substâncias Luminescentes/química , Camundongos , Nanopartículas/química , Neoplasias/terapia , Paclitaxel/química , Polietilenoglicóis/química , Compostos de Tungstênio/químicaRESUMO
Suspensions of nanoparticles (NPs) in aqueous solutions hold promise in many research fields, including energy applications, water desalination, and nanomedicine. The ability to tune NP interactions, and thereby to modulate the NP self-assembly process, holds the key to rationally synthesize NP suspensions. However, traditional models obtained by coupling the DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory of NP interactions, or suitable modifications of it, with the kinetic theory of colloidal aggregation are inadequate to precisely model NP self-assembly because they neglect hydration forces and discrete-size effects predominant at the nanoscale. By synergistically blending molecular dynamics and stochastic dynamics simulations with continuum theories, we develop a multi-scale (MS) model, which is able to accurately predict suspension stability, timescales for NP aggregation, and macroscopic properties (e.g., the thermal conductivity) of bare and surfactant-coated NP suspensions, in good agreement with the experimental data. Our results enable the formulation of design rules for engineering NP aqueous suspensions in a wide range of applications.
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Radiation therapy is a primary treatment modality for many forms of cancer. Normally, the highest tolerable dose of ionizing radiation is used to treat tumors, but limitations imposed by normal tissue complications present challenges for local tumor control. In light of this, a class of compounds called radio-sensitizers have been developed to enhance the effectiveness of radiation. Many of these are small molecule drugs found to interact favorably with radiation therapy, but recent advances have been made using nanoparticles as radio-sensitizers. Herein, we report the utilization of radio-luminescent calcium tungstate nanoparticles that emit photoelectrons, UV-A, and visible light during X-ray irradiation, acting as effective radio-sensitizers ("Radio Luminescence Therapy"). In addition, a folic acid-functionalized form of these nanoparticles was shown to enhance radio-sensitization in vitro and in murine models of head and neck cancer. Folic acid-functionalized particles were found to decrease UV-A-induced clonogenic cell survival relative to nonfunctionalized particles. Several possible mechanisms were explored, and the folic acid-functionalized particles were found to mediate this increase in efficacy likely by activating pro-proliferative signaling through folate's innate mitogenic activity, leading to decreased repair of UV-A-induced DNA lesions. Finally, a clinical case study of a canine sarcoma patient demonstrated the initial safety and feasibility of translating these folic acid-functionalized particles into the clinic as radio-sensitizers in the treatment of spontaneous tumors.