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The adsorption of cationic peptide JM21 onto different mesoporous silica nanoparticles (MSNs) from an aqueous solution was studied as a function of pH. In agreement with the literature, the highest loading degrees could be achieved at pH close to the isoelectric point of the peptide where the peptide-peptide repulsion is minimum. However, mesopore size, mesopore geometry, and surface polarity all had an influence on the peptide adsorption in terms of both affinity and maximum loading at a given pH. This adsorption behavior could largely be explained by a combination of pH-dependent electrostatic interactions and confinement effects. It is demonstrated that hydrophobic interactions enhance the degree of peptide adsorption under pH conditions where the electrostatic attraction was absent in the case of mesoporous organosilica nanoparticles (MONs). The lower surface concentration of silanol groups for MON led to a lower level of peptide adsorption under optimum pH conditions compared to all-silica particles. Finally, the study confirmed the protective role of MSNs in preserving the biological activity of JM#21 against enzymatic degradation, even for large-pore MSNs, emphasizing their potential as nanocarriers for therapeutic peptides. By integrating experimental findings with theoretical modeling, this research elucidates the complex interplay of factors that influence peptide-silica interactions, providing vital insights for optimizing peptide loading and stabilization in biomedical applications.
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Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Peptídeos/química , Nanopartículas/química , Porosidade , Portadores de Fármacos/químicaRESUMO
In a previous contribution we described the formation of silica nanostructures in dye-stabilized nanoemulsions from tetraethyl orthosilicate droplets in water. Depending on the type of dye, either capsules (crystal violet, CV) or nanoparticles (congo red, CR) are formed. The thorough study of the sol-gel process uses a combination of time- and/or temperature-resolved small-angle X-ray scattering, transmission electron microscopy, and 1H NMR spectroscopy to elucidate the detailed kinetics and mechanism of structure formation. In both cases, small nuclei of 1.5-2 nm are formed, followed by either a fast cluster-cluster (CV) or a much slower monomer-cluster aggregation (CR). The former leads to a cross-linked network and finally to patchy capsules, while the latter leads to individual nanoparticles (SNPs). From an Avrami plot it can be deduced that the SNPs are formed by an interface-controlled one-dimensional growth process. The mechanisms are based on the different local environments at the oil-water interface, which is either slightly acidic (CV) or fairly basic (CR). The kinetics differ by a factor between 3 and 20 and are presumably caused by the different mobility of the catalyzing species H+ or OH-.
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OBJECTIVES: A common limitation of all 1H contrast agents is that they only allow indirect visualization through modification of the intrinsic properties of the tissue, making quantification of this effect challenging. 19F compounds, on the contrary, are measured directly, without any background signal. There is a linear relationship between the amount of 19F spins and the intensity of the signal. However, non-uniformity of the radiofrequency field may lead to errors in the quantified 19F signal and should be carefully addressed for any quantitative imaging. MATERIALS AND METHODS: Adaptation of the previously introduced [Formula: see text] mapping technique to the problem of quantifying the 19F signal from perfluoro-15-crown-5-ether (PFCE) is proposed in this work. Initial evaluation of the proposed technique simultaneously accounting for transmit [Formula: see text] and receive [Formula: see text] field inhomogeneities is performed in a PFCE phantom. As a proof of concept, in vivo quantification of the 19F signal is performed in a murine model after application of custom-designed hollow mesoporous silica spheres (HMSS) loaded with PFCE. RESULTS: A phantom experiment clearly shows that only compensation for both transmit and receive characteristics outperforms inaccurate quantification based on the non- or partly-corrected signal intensities. Furthermore, an optimized protocol is proposed for in vivo application. CONCLUSION: The proposed [Formula: see text]/[Formula: see text] mapping technique represents a simple to implement and easy-to-use solution for quantification of the 19F signal from PFCE in the presence of B1-field inhomogeneities.
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Éteres de Coroa/química , Imagem por Ressonância Magnética de Flúor-19 , Flúor/química , Animais , Meios de Contraste , Humanos , Processamento de Imagem Assistida por Computador , Fígado/diagnóstico por imagem , Camundongos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Dióxido de SilícioRESUMO
The adsorption of serum proteins, leading to the formation of a biomolecular corona, is a key determinant of the biological identity of nanoparticles in vivo. Therefore, gaining knowledge on the formation, composition, and temporal evolution of the corona is of utmost importance for the development of nanoparticle-based therapies. Here, it is shown that the use of super-resolution optical microscopy enables the imaging of the protein corona on mesoporous silica nanoparticles with single protein sensitivity. Particle-by-particle quantification reveals a significant heterogeneity in protein absorption under native conditions. Moreover, the diversity of the corona evolves over time depending on the surface chemistry and degradability of the particles. This paper investigates the consequences of protein adsorption for specific cell targeting by antibody-functionalized nanoparticles providing a detailed understanding of corona-activity relations. The methodology is widely applicable to a variety of nanostructures and complements the existing ensemble approaches for protein corona study.
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Microscopia/métodos , Nanopartículas/química , Coroa de Proteína/química , Adsorção , Animais , Bovinos , Cinética , Porosidade , Soroalbumina Bovina/química , Dióxido de Silício/química , Propriedades de Superfície , Fatores de TempoRESUMO
Pickering emulsions with a remarkable transmittance of up to 86% across the visible spectrum have been prepared without adjusting the refractive index (RI) of the stabilizing particles to those of the aqueous and oil phases. Commercially available hydrophilic silica particles with a diameter of 20 nm, which are hydrophobized partially in situ, were used to stabilize water droplets with diameters below 400 nm in IsoparM. In this system, the stabilizing particles and the emulsion droplets act as one single scattering object, which renders RI-matching of the particles unnecessary. By either evaporation of some water from the droplets or addition of an appropriate organic liquid to the oil phase, it is possible to match the RI of the droplets (aqueous phase + particles) with that of the continuous phase, which minimizes scattering and results in highly transparent emulsions.
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Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Glucose/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Receptores Notch/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Antineoplásicos/farmacologia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/química , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The convergence of biofabrication with nanotechnology is largely unexplored but enables geometrical control of cell-biomaterial arrangement combined with controlled drug delivery and release. As a step towards integration of these two fields of research, this study demonstrates that modulation of electrostatic nanoparticle-polymer and nanoparticle-nanoparticle interactions can be used for tuning nanoparticle release kinetics from 3D printed hydrogel scaffolds. This generic strategy can be used for spatiotemporal control of the release kinetics of nanoparticulate drug vectors in biofabricated constructs.
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We propose a novel analytical method for mercury (Hg) trace determination based on direct Hg preconcentration from aqueous solution onto a gold nanoparticle-decorated silica monolith (AuNP@SiO2). Detection of Hg is performed after thermal desorption by means of atomic fluorescence spectrometry. This new methodology benefits from reagent-free, time- and cost-saving procedure, due to most efficient solid-phase adsorbent and results in high sensitive quantification. The excellent analytical performance of the whole procedure is demonstrated by a limit of detection as low as 1.31 ng L(-1) for only one-min accumulation duration. A good reproducibility with standard deviations ≤5.4% is given. The feasibility of the approach in natural waters was confirmed by a recovery experiment in spiked seawater with a recovery rate of 101%. Moreover, the presented method was validated through reference analysis of a submarine groundwater discharge sample by cold vapor-atomic fluorescence spectrometry resulting in a very good agreement of the found values. Hence the novel method is a very promising new tool for low-level Hg monitoring in natural waters providing easy-handling on-site preconcentration, reagent-free stabilization as well as reagent-free, highly sensitive detection.
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Ouro/química , Mercúrio/análise , Nanopartículas Metálicas/química , Poluentes Químicos da Água/análise , Adsorção , Microscopia Eletrônica de Varredura , Reprodutibilidade dos TestesRESUMO
Dysregulation of the CXCL12/CXCR4 axis is implicated in autoimmune, inflammatory, and oncogenic diseases, positioning CXCR4 as a pivotal therapeutic target. We evaluated optimized variants of the specific endogenous CXCR4 antagonist, EPI-X4, addressing existing challenges in stability and potency. Our structure-activity relationship study investigates the conjugation of EPI-X4 derivatives with long-chain fatty acids, enhancing serum albumin interaction and receptor affinity. Molecular dynamic simulations revealed that the lipid moieties stabilize the peptide-receptor interaction through hydrophobic contacts at the receptor's N-terminus, anchoring the lipopeptide within the CXCR4 binding pocket and maintaining essential receptor interactions. Accordingly, lipidation resulted in increased receptor affinities and antagonistic activities. Additionally, by interacting with human serum albumin lipidated EPI-X4 derivatives displayed sustained stability in human plasma and extended circulation times in vivo. Selected candidates showed significant therapeutic potential in human retinoblastoma cells in vitro and in ovo, with our lead derivative exhibiting higher efficacies compared to its non-lipidated counterpart. This study not only elucidates the optimization trajectory for EPI-X4 derivatives but also underscores the intricate interplay between stability and efficacy, crucial for delineating their translational potential in clinical applications.
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Mesoporous silica nanoparticles, MSNs, have emerged as an interesting carrier for drugs in vitro and in vivo. The particles are typically used in a surface functionalized form, where functional silanes or other covalently linked surface functions are used to provide anchoring sites for additional functionalities like targeting groups, imaging agents, and drugs. Here, we report results related to extra- and intracellular degradation of silica nanoparticles using multilabeled nonporous silica core-mesoporous silica shell-surface hyperbranched poly(ethylene imine) shell nanoparticles as model particles. Different fluorophores have been selectively covalently linked to different regions of the particles in order to study the particle degradation in detail under in vitro conditions in human SAOS-2 cells. A novel, quantitative method for nanoparticle degradation evaluation based on confocal fluorescence microscopy is applied. Our results suggest that the core-shell-shell MSNs degrade at a higher rate inside cells as compared to outside cells, which is of high importance for further application of this class of drug carriers.
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Portadores de Fármacos/química , Iminas/química , Nanopartículas/química , Polietilenos/química , Dióxido de Silício/química , Linhagem Celular , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/farmacocinética , Humanos , Iminas/farmacocinética , Teste de Materiais , Nanopartículas/ultraestrutura , Nanotecnologia , Polietilenos/farmacocinética , Dióxido de Silício/farmacocinética , Propriedades de SuperfícieRESUMO
Mesoporous silica nanoparticles (MSNs) have emerged as a very promising drug delivery platform. However, multi-step synthesis and surface functionalization protocols rise the hurdle for translation of this promising drug delivery platform to the clinic. Furthermore, surface functionalization aiming at enhancing the blood circulation time, typically through surface functionalization with poly(ethylene glycol) (PEG) (PEGylation), has repeatedly been shown to be detrimental for the drug loading levels that can be achieved. Here, we present results related to sequential adsorptive drug loading and adsorptive PEGylation, where the conditions can be chosen so that the drug desorption during PEGylation is minimized. At the heart of the approach is the high solubility of PEG both in water and in apolar solvents, which makes it possible to use a solvent for PEGylation in which the drug exhibits a low solubility, as demonstrated here for two model drugs, one being water soluble and the other not. Analysis of the influence of PEGylation on the extent of serum protein adsorption underline the promise of the approach, and the results also allow the adsorption mechanisms to be elaborated. Detailed analysis of the adsorption isotherms enables determination of the fractions of PEG residing on the outer particle surfaces in comparison to inside the mesopore systems, and also makes it possible to determine the PEG conformation on the outer particle surfaces. Both parameters are directly reflected in the extent of protein adsorption to the particles. Finally, the PEG coating is shown to be stable on time-scales compatible with intravenous drug administration, which is why we are convinced that the presented approach or modifications thereof will pave the way for faster translation of this drug delivery platform to the clinic.
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Nanopartículas , Dióxido de Silício , Adsorção , Sistemas de Liberação de Medicamentos , Solventes , Água , Proteínas Sanguíneas , Portadores de Fármacos , PorosidadeRESUMO
An efficient nanoparticulate drug carrier intended for chemotherapy based on intravenous administration must exhibit a long enough blood circulation time, a good penetrability into the tumour volume, as well as an efficient uptake by cancer cells. Limiting factors for the therapeutic outcome in vivo are recognition of the nanoparticles as foreign objects, which triggers nanoparticle uptake by defence organs rich in macrophages, e.g. liver and spleen, on the time-scale of accumulation and uptake in/by the tumour. However, the development of nanomedicine towards efficient nanoparticle-based delivery to solid tumours is hampered by the lack of simple, reproducible, cheap, and predictive means for early identification of promising nanoparticle formulations. The surface chemistry of nanoparticles is known to be the most important determinant for the biological fate of nanoparticles, as it influences the extent of serum protein adsorption, and also the relative composition of the protein corona. Here we preliminarily evaluate an extremely simple screening method for nanoparticle surface chemistry pre-optimization based on nanoparticle uptake in vitro by PC-3 cancer cells and THP-1 macrophages. Only when both selectivity for the cancer cells as well as the extent of nanoparticle uptake are taken into consideration do the in vitro results mirror literature results obtained for small animal models. Furthermore, although not investigated here, the screening method does also lend itself to the study of actively targeted nanoparticles.
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Nanopartículas , Neoplasias , Coroa de Proteína , Animais , Neoplasias/tratamento farmacológico , Nanopartículas/química , Portadores de Fármacos , Proteínas Sanguíneas/química , Fígado/metabolismo , Coroa de Proteína/químicaRESUMO
Silica nanoparticles (SNP) have gained tremendous attention in the recent decades. They have been used in many different biomedical fields including diagnosis, biosensing and drug delivery. Medical uses of SNP for anti-cancer, anti-microbial and theranostic applications are especially prominent due to their exceptional performance to deliver many different small molecules and recently biologics (mRNA, siRNA, antigens, antibodies, proteins, and peptides) at targeted sites. The physical and chemical properties of SNP such as large specific surface area, tuneable particle size and porosity, excellent biodegradability and biocompatibility make them an ideal drug delivery and diagnostic platform. Based on the available data and the pre-clinical performance of SNP, recent interest has driven these innovative materials towards clinical application with many of the formulations already in Phase I and Phase II trials. Herein, the progress of SNP in biomedical field is reviewed, and their safety aspects are analysed. Importantly, we critically evaluate the key structural characteristics of SNP to overcome different biological barriers including the blood-brain barrier (BBB), skin, tumour barrier and mucosal barrier. Future directions, potential pathways, and target areas towards rapid clinical translation of SNP are also recommended.
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Nanopartículas , Neoplasias , Humanos , Portadores de Fármacos/química , Dióxido de Silício , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , PorosidadeRESUMO
Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo. The negatively charged, non-toxic particles showed different accumulation behavior over time in healthy mice and in mice with dextran sulfate sodium (DSS)-induced intestinal inflammation. PEGylated particles were shown to accumulate in the lower intestinal tract of healthy animals, whereas inflammation promoted retention of HA-functionalized particles in this area. Overall systemic absorption was low. However, some particles were detected in organs of mice with DSS-induced colitis, especially in the case of MSN-PEG. The in vivo findings were connected to surface chemistry-related differences in particle adhesion on Caco-2/Raji and mucus-producing Caco-2/Raji/HT29 cell co-culture epithelial models in vitro. While the particle adhesion behavior in vivo was mirrored in the in vitro results, this was not the case for the resorption results, suggesting that the in vitro model does not fully reflect the erosion of the inflamed epithelial tissue. Overall, our study demonstrates the possibility to modulate accumulation and retention of MSNs in the GIT of mice with and without inflammation through surface functionalization, which has important implications for the formulation of nanoparticle-based delivery systems for oral delivery applications.
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Colite , Nanopartículas , Humanos , Camundongos , Animais , Sistemas de Liberação de Medicamentos/métodos , Células CACO-2 , Dióxido de Silício , Colite/induzido quimicamente , Colite/tratamento farmacológico , Polietilenoglicóis , Inflamação , Sulfato de DextranaRESUMO
Nanoparticle based permeation enhancers have the potential to improve the oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve the intestinal permeability of peptides and proteins via transient opening of the gut epithelium. In this study, we have developed small-sized (â¼60 nm) virus-like silica nanoparticles (VSNP) as a reversible and next generation non-toxic permeation enhancer for oral delivery of biologics. Our results show that the anionic VSNP showed a better permeation-enhancing effect than the same sized spherical Stöber silica nanoparticles (â¼60 nm) by enhancing the apparent insulin permeability by 1.3-fold in the Caco-2 monolayer model and by 1.2-fold in the Caco-2/MTX-HT-29 co-culture model. In vivo experiments in healthy mice demonstrated that anionic VSNP significantly enhanced the permeation of fluorescently labelled 4 kDa dextran after oral administration compared to Stöber nanoparticles and positively charged VSNP. The results indicated that the nanoscale surface roughness is an important consideration when designing nanoparticle-based permeation enhancers. Overall, our study shows for the first time that small-sized (â¼60 nm) VSNP with nanoscale surface roughness can be used as a non-toxic permeation enhancer for oral delivery of therapeutic peptides and proteins.
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Nanopartículas , Dióxido de Silício , Humanos , Camundongos , Animais , Células CACO-2 , Dióxido de Silício/metabolismo , Mucosa Intestinal/metabolismo , Peptídeos/química , Administração Oral , Nanopartículas/químicaRESUMO
We have fabricated hybrid devices in the form of indium tin oxide/titanium dioxide/poly(3-hexylthiophene):[6,6]-phenyl C61 butyric acid methyl ester/copper (ITO/TiO(2)/P3HT:PCBM/Cu) to clarify the impact of the TiO(2)/P3HT:PCBM interface on the charge transport using the charge extraction by linearly increasing voltage (CELIV) technique. We found that a large equilibrium charge reservoir is accumulated at negative offsets at the TiO(2)/P3HT:PCBM interface leading to space charge limited extraction current (SCLC) transients. We show analytically the SCLC transient response and compare the experimental data to calculated SCLC at a linearly increasing voltage. The theoretical calculations indicate that the large charge reservoir at negative offset voltages is due to thermally generated charges combined with poor hole extraction at the ITO/TiO(2) contact, due to the hole blocking character of TiO(2).
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Notch signaling, a key regulator of stem cells, is frequently overactivated in cancer. It is often linked to aggressive forms of cancer, evading standard treatment highlighting Notch as an exciting therapeutic target. Notch is in principle "druggable" by γ-secretase inhibitors (GSIs), inhibitory peptides and antibodies, but clinical use of Notch inhibitors is restricted by severe side effects and there is a demand for alternative cancer-targeted therapy. Here, we present a novel approach, using imagable mesoporous silica nanoparticles (MSNPs) as vehicles for targeted delivery of GSIs to block Notch signaling. Drug-loaded particles conjugated to targeting ligands induced cell-specific inhibition of Notch activity in vitro and exhibited enhanced tumor retainment with significantly improved Notch inhibition and therapeutic outcome in vivo. Oral administration of GSI-MSNPs controlled Notch activity in intestinal stem cells further supporting the in vivo applicability of MSNPs for GSI delivery. MSNPs showed tumor accumulation and targeting after systemic administration. MSNPs were biocompatible, and particles not retained within the tumors, were degraded and eliminated mainly by renal excretion. The data highlights MSNPs as an attractive platform for targeted drug delivery of anticancer drugs with otherwise restricted clinical application, and as interesting constituents in the quest for more refined Notch therapies.
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Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/uso terapêutico , Receptores Notch/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular , Feminino , Humanos , Camundongos , Nanopartículas/administração & dosagem , Porosidade , Receptores Notch/metabolismo , Dióxido de Silício/administração & dosagem , Dióxido de Silício/uso terapêuticoRESUMO
Mesoporous silica nanoparticles (MSN) are promising drug vectors due to their high drug loading capacities, degradability under biologically relevant conditions. The dissolution of MSN has been the focus of several recent studies, most of which have, however, been carried out in the absence of proteins, and do therefore not reflect the conditions prevailing during in vitro or in vivo administration of the particles. Furthermore, typically the dissolution studies are limited with respect to the range of MSN concentrations applied. Here, we report results related to the dissolution kinetics and structural particle evolution for MCM-48 MSN carried out in the presence of proteins, and where the particle concentration has been used as a parameter to cover typical concentrations used in in vitro and in vivo studies involving MSNs. Proteins adsorbing to the MSN surface form a diffusion limiting layer that leads to the intermediate formation of core-shell structured particles upon dissolution. Here, the protein concentration controls the kinetics of this process, as the amount of protein adsorbing to the MSN increase with increasing protein concentration. The results thus also imply that the MSN dissolution kinetics is faster under normally applied in vitro conditions as compared to what can be expected under full serum conditions.
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Nanopartículas , Dióxido de Silício , Portadores de Fármacos , Porosidade , SolubilidadeRESUMO
Li-rich layered oxides (LRLO) with specific energies beyond 900â Wh kg-1 are one promising class of high-energy cathode materials. Their high Mn-content allows reducing both costs and the environmental footprint. In this work, Co-free Li1.2 Mn0.6 Ni0.2 O2 was investigated. A simple water and acid treatment step followed by a thermal treatment was applied to the LRLO to reduce surface impurities and to establish an artificial cathode electrolyte interface. Samples treated at 300 °C show an improved cycling behavior with specific first cycle capacities of up to 272â mAh g-1 , whereas powders treated at 900 °C were electrochemically deactivated due to major structural changes of the active compounds. Surface sensitive analytical methods were used to characterize the structural and chemical changes compared to the bulk material. Online DEMS measurements were conducted to get a deeper understanding of the effect of the treatment strategy on O2 and CO2 evolution during electrochemical cycling.
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Mercury detection in humic matter-containing natural waters is often associated with environmental harmful substances for sample preparation. Herein we report an approach based on photoactive titanium dioxide films with embedded gold nanoparticles (AuNP@TiO2 dipstick) for chemical-free sample preparation and mercury preconcentration. For this purpose, AuNPs are immobilized onto a silicon wafer and further covered with a thin photoactive titanium dioxide layer. The AuNPs allow the preconcentration of Hg traces via amalgamation, while TiO2 acts as a protective layer and, at the same time, as a photocatalyst for UV-C radiation-based sample pretreatment. Humic matter, often present in natural waters, forms stabile complexes with Hg and so hinders its preconcentration prior to detection, causing a minor recovery. This problem is solved here by irradiation during Hg preconcentration onto the photoactive dipstick, resulting in a limit of detection as low as 0.137 ng L-1 using atomic fluorescence spectrometry (AFS). A 5 min preconcentration step is sufficient to obtain successful recovery of Hg traces from waters with up to 10 mg L-1 DOC. The feasibility of the approach was demonstrated by the determination of Hg traces in Danube river water. The results show no significant differences in comparison with standard cold vapor-atomic fluorescence spectrometry (CV-AFS) measurements of the same sample. Hence, this new AuNP@TiO2 dipstick provides a single-step sample preparation and preconcentration approach that combines sustainability with high analytical sensitivity and accuracy.