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Zwitterionic coatings are an efficient strategy for preventing biomolecule adsorption and enhancing nanoparticle stability in solution. The properties of zwitterions and other antifouling materials, including suppression of nonspecific adsorption and improved colloidal stability of nanoparticles, are believed to derive from their electroneutral and highly hydrophilic nature. Among different zwitterions, short sulfobetaines have been demonstrated to be effective in preventing protein adsorption onto several nanoparticles and providing enhanced colloidal stability. Although zwitterionic sulfobetaine silane (ZS) is electrically neutral, the negatively charged zwitterionic sulfobetaine-functionalized silica nanoparticles (ZS@SiO2NPs) exhibit a similar ζ-potential to nonfunctionalized silica nanoparticles (SiO2NPs). In this work, we present a thorough comprehension of the surface properties of ZS@SiO2NPs, which encompasses the development of meticulous functionalization procedures, detailed characterization approaches, and cutting-edge modeling to address the questions that persist regarding the surface features of ZS@SiO2NPs. The negative charge of ZS@SiO2NPs is due to the stabilization of siloxide from residual surface silanols by the quaternary amine in the sulfobetaine structure. Consequently, we infer that zero-charge ZS@SiO2NPs are unlikely to be obtained since this stabilization increases the dissociation degree of surface silanols, increasing the overall structure negative charge. Additionally, colloidal stability was evaluated in different pH and ionic strength conditions, and it was found that ZS@SiO2NPs are more stable at higher ionic strengths. This suggests that the interaction between ZS and salt ions prevents the aggregation of ZS@SiO2NPs. Together, these results shed light on the nature of the ZS@SiO2NP negative charge and possible sources for the remarkable colloidal stability of zwitterionic nanoparticles in complex media.

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Most nanomaterial-based medicines are intravenously applied since oral administration comprises challenging-related biological obstacles, such as interactions with distinct digestive fluids and their transport through the intestinal barrier. Moreover, there is a lack of nanoparticle-based studies that faithfully consider the above-cited obstacles and boost oral-administered nanomedicines' rational design. In this study, the physicochemical stability of fluorescent model silica nanoparticles (f-SiO2NPs) passing through all simulated gastrointestinal fluids (salivary, gastric, and intestinal) and their absorption and transport across a model human intestinal epithelium barrier are investigated. An aggregation/disaggregation f-SiO2NPs process is identified, although these particles remain chemically and physically stable after exposure to digestive fluids. Further, fine imaging of f-SiO2NPs through the absorption and transport across the human intestinal epithelium indicates that nanoparticle transport is time-dependent. The above-presented protocol shows tremendous potential for deciphering fundamental gastrointestinal nanoparticles' evolution and can contribute to rational oral administration-based nanomedicine design.

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Assuntos

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The mesoporous SBA-15 material was surface-functionalized with amino and carboxylic acid groups and used as a platform to investigate the interaction of these chemical groups with tetracycline, kanamycin, and ampicillin antibiotics. The interactions between the antibiotic and the functionalized surfaces were characterized using two-dimensional 1H-13C HETCOR CP MAS and FTIR spectroscopy and indicated that -COO- NH3 + bondings had been formed between chemical groups on the silica surface and drug molecules. The surface modification resulted in higher kanamycin and ampicillin loadings and a slow-release rate, and all synthesized systems showed antibacterial activity against susceptible Escherichia coli bacteria. Almost total death of bacteria was obtained using a few ppm of tetracycline- and kanamycin-loaded systems, whereas the ampicillin-loaded one showed lower bactericidal activity than free ampicillin.

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HYPOTHESIS: Hydrophobicity and the presence or absence of charge in phenol derivatives are relevant on the rheology and phase behavior when they are assembled with a cationic surfactant, forming wormlike micelles. The incorporation of phenols with a greater number of rings into the micellar palisade is entropically favored, but a solubilization limit or coacervation are two paths followed by the solutions, depending on the electrical nature of the aromatic co-solutes. EXPERIMENTS: The investigations were carried out with systems formed by a fixed concentration of hexadecyltrimethylammonium bromide (CTAB) and increasing concentrations of neutral phenols (1-naphthol, 2-naphthol, 2,3-dihydroxynaphthalene and R and S-binol) and with their corresponding phenolate derivatives. The monophasic limits of the systems were established, as well as their linear and non-linear rheology. The structural investigation of the coacervates formed with the phenolates were done using SAXS and Cryo-TEM. FINDINGS: The zero-shear viscosity of the solutions reaches maxima values close to the solubility limit of the aromatics, which depends on the numbers of rings and hydroxyl groups (position and number). However, when the correspondent ionized phenols were investigated, beyond the maxima values for the zero-shear viscosity, liquid-liquid biphasic systems are formed, in which the upper phase contains a coacervate, associated with branched wormlike micelles. However, when the ratio between phenolate and CTAB is around 3:1 the coacervate evolves to a lamellar structure.

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Protein corona formation and nanoparticles' aggregation have been heavily discussed over the past years since the lack of fine-mapping of these two combined effects has hindered the targeted delivery evolution and the personalized nanomedicine development. We present a multitechnique approach that combines dynamic light and small-angle X-ray scattering techniques with cryotransmission electron microscopy in a given fashion that efficiently distinguishes protein corona from aggregates formation. This methodology was tested using ∼25 nm model silica nanoparticles incubated with either model proteins or biologically relevant proteomes (such as fetal bovine serum and human plasma) in low and high ionic strength buffers to precisely tune particle-to-protein interactions. In this work, we were able to differentiate protein corona, small aggregates formation, and massive aggregation, as well as obtain fractal information on the aggregates reliably and straightforwardly. The strategy presented here can be expanded to other particle-to-protein mixtures and might be employed as a quality control platform for samples that undergo biological tests.

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The global pandemic scenario has definitely pushed the scientific community to develop COVID-19 vaccines at unprecedented speed. Nevertheless, a worldwide vaccination campaign is still far from being achieved, making the usual precautionary measures as necessary as at the beginning of the outbreak. Many aspects of the SARS-CoV-2 infectious potential and disease severity do not solely rely on interactions at the molecular level but also on physical-chemical parameters that often involve nanoscale effects. Here the SARS-CoV-2 journey to infect a susceptible host is reviewed, focusing on the nanoscale aspects that play a role in the viral infectivity and disease progression. These nanoscale-driven interactions are essential to establish mitigation-related strategies.

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Assuntos

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Freeze-drying of nanoparticle suspensions is capable of generating stable nanoformulations with improved storage times and easier transportation. Nonetheless, nanoparticle aggregation is likely induced during freeze-drying, which reduces its redispersibility upon reconstitution and leads to undesirable effects such as non-specific toxicity and impaired efficacy. In this work, bovine serum albumin (BSA) is described as a suitable protectant for silica nanoparticles (SNPs), which result in solid structures with excellent redispersibility and negligible signs of aggregation even when longer storage times are considered. We experimentally demonstrated that massive system aggregation can be prevented when a saturated BSA corona around the nanoparticle is formed before the lyophilization process. Furthermore, the BSA corona is able to suppress non-specific interactions between these nanoparticles and biological systems, as evidenced by the lack of residual cytotoxicity, hemolytic activity and opsonin adsorption. Hence, BSA can be seriously considered for industry as an additive for nanoparticle freeze-drying since it generates solid and redispersible nanoformulations with improved biocompatibility.

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Zwitterionic molecules are known to resist nonspecific protein adsorption and have been proposed as an alternative to the widely used polyethylene glycol. Recently, zwitterionic-like nanoparticles were created from the coimmobilization of positive and negative ligands, resulting in surfaces that also prevent protein corona formation while keeping available sites for bioconjugation. However, it is unclear if they are able to keep their original properties when immersed in biological environments while retaining a toxicity-free profile, indispensable features before considering these structures for clinics. Herein, we obtained optimized zwitterionic-like silica nanoparticles from the functionalization with varying ratios of THPMP and DETAPTMS organosilanes and investigated their behavior in realistic biological milieu. The generated zwitterionic-like particle was able to resist single-protein adsorption, while the interaction with a myriad of serum proteins led to significant loss of colloidal stability. Moreover, the zwitterionic particles presented poor hemocompatibility, causing considerable disruption of red blood cells. Our findings suggest that the exposure of ionic groups allows these structures to directly engage with the environment and that electrostatic neutrality is not enough to grant low-fouling and stealth properties.