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Dual-functionalized architecture enables stable and tumor cell-specific SiO<sub>2</sub>NPs in complex biological fluids

Most commercial anticancer nanomedicines are administered intravenously. This route is fast and precise as the drug enters directly into the systemic circulation, without undergoing absorption processes. When nanoparticles come into direct contact with the blood, however, they interact with physiological components that can induce colloidal destabilization and/or changes in their original biochemical identity, compromising their ability to selectively accumulate at target sites. In this way, these systems usually lack active targeting, offering limited therapeutic effectiveness. In the literature, there is a paucity of in-depth studies in complex environments to evaluate nanoparticle stability, protein corona formation, hemolytic activity, and targeting capabilities. To address this issue, fluorescent silica nanoparticles (SiO2NPs) are here functionalized with zwitterionic (kinetic stabilizer) and folate groups (targeting agent) to provide selective interaction with tumor cell lines in biological media. The stability of these dually functionalized SiO2NPs is preserved in unprocessed human plasma while yielding a decrease in the number of adsorbed proteins. Experiments in murine blood further proved that these nanoparticles are not hemolytic. Remarkably, the functionalized SiO2NPs are more internalized by tumor cells than their healthy counterparts. Investigations of this nature play a crucial role in garnering results with greater reliability, allowing the development of nanoparticle-based pharmaceutical drugs that exhibit heightened efficacy and reduced toxicity for medical purposes.

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AI-assisted models to predict chemotherapy drugs modified with C60 fullerene derivatives.

Employing quantitative structure-activity relationship (QSAR)/ quantitative structure-property relationship (QSPR) models, this study explores the application of fullerene derivatives as nanocarriers for breast cancer chemotherapy drugs. Isolated drugs and two drug-fullerene complexes (i.e., drug-pristine C60 fullerene and drug-carboxyfullerene C60-COOH) were investigated with the protein CXCR7 as the molecular docking target. The research involved over 30 drugs and employed Pearson's hard-soft acid-base theory and common QSAR/QSPR descriptors to build predictive models for the docking scores. Energetic descriptors were computed using quantum chemistry at the density functional-based tight binding DFTB3 level. The results indicate that drug-fullerene complexes interact more with CXCR7 than isolated drugs. Specific binding sites were identified, with varying locations for each drug complex. Predictive models, developed using multiple linear regression and IBM Watson artificial intelligence (AI), achieved mean absolute percentage errors below 12%, driven by AI-identified key variables. The predictive models included mainly quantitative descriptors collected from datasets as well as computed ones. In addition, a water-soluble fullerene was used to compare results obtained by DFTB3 with a conventional density functional theory approach. These findings promise to enhance breast cancer chemotherapy by leveraging fullerene-based drug nanocarriers.

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Introducing third-generation periodic table descriptors for nano-qRASTR modeling of zebrafish toxicity of metal oxide nanoparticles.

Metal oxide nanoparticles (MONPs) are widely used in medicine and environmental remediation because of their unique properties. However, their size, surface area, and reactivity can cause toxicity, potentially leading to oxidative stress, inflammation, and cellular or DNA damage. In this study, a nano-quantitative structure-toxicity relationship (nano-QSTR) model was initially developed to assess zebrafish toxicity for 24 MONPs. Previously established 23 first- and second-generation periodic table descriptors, along with five newly proposed third-generation descriptors derived from the periodic table, were employed. Subsequently, to enhance the quality and predictive capability of the nano-QSTR model, a nano-quantitative read across structure-toxicity relationship (nano-qRASTR) model was created. This model integrated read-across descriptors with modeled descriptors from the nano-QSTR approach. The nano-qRASTR model, featuring three attributes, outperformed the previously reported simple QSTR model, despite having one less MONP. This study highlights the effective utilization of the nano-qRASTR algorithm in situations with limited data for modeling, demonstrating superior goodness-of-fit, robustness, and predictability (R 2 = 0.81, Q 2 LOO = 0.70, Q 2 F1/R 2 PRED = 0.76) compared to simple QSTR models. Finally, the developed nano-qRASTR model was applied to predict toxicity data for an external dataset comprising 35 MONPs, addressing gaps in zebrafish toxicity assessment.

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Direct electron beam writing of silver using a β-diketonate precursor: first insights.

Direct electron beam writing is a powerful tool for fabricating complex nanostructures in a single step. The electron beam locally cleaves the molecules of an adsorbed gaseous precursor to form a deposit, similar to 3D printing but without the need for a resist or development step. Here, we employ for the first time a silver β-diketonate precursor for focused electron beam-induced deposition (FEBID). The used compound (hfac)AgPMe3 operates at an evaporation temperature of 70-80 °C and is compatible with commercially available gas injection systems used in any standard scanning electron microscope. Growth of smooth 3D geometries could be demonstrated for tightly focused electron beams, albeit with low silver content in the deposit volume. The electron beam-induced deposition proved sensitive to the irradiation conditions, leading to varying compositions of the deposit and internal inhomogeneities such as the formation of a layered structure consisting of a pure silver layer at the interface to the substrate covered by a deposit layer with low silver content. Imaging after the deposition process revealed morphological changes such as the growth of silver particles on the surface. While these effects complicate the application for 3D printing, the unique deposit structure with a thin, compact silver film beneath the deposit body is interesting from a fundamental point of view and may offer additional opportunities for applications.

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Effect of wavelength and liquid on formation of Ag, Au, Ag/Au nanoparticles via picosecond laser ablation and SERS-based detection of DMMP.

The present study investigates the effects of input wavelength (1064, 532, and 355 nm) and surrounding liquid environment (distilled water and aqueous NaCl solution) on the picosecond laser ablation on silver (Ag), gold (Au), and Ag/Au alloy targets. The efficacy of the laser ablation technique was meticulously evaluated by analyzing the ablation rates, surface plasmon resonance peak positions, and particle size distributions of the obtained colloids. The nanoparticles (NPs) were characterized using the techniques of UV-visible absorption, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Furthermore, NPs of various sizes ranging from 6 to 35 nm were loaded onto a filter paper by a simple and effective drop-casting approach to achieve flexible surface-enhanced Raman spectroscopy (SERS) substrates/sensors. These substrates were tested using a simple, portable Raman device to identify various hazardous chemicals (malachite green, methyl salicylate, and thiram). The stability of the substrates was also systematically investigated by determining the decay percentages in the SERS signals over 60 days. The optimized SERS substrate was subsequently employed to detect chemical warfare agent (CWA) simulants such as methyl salicylate (a CWA simulant for sulfur mustard) and dimethyl methyl phosphonate (has some structural similarities to the G-series nerve agents) at different laser excitations (325, 532, and 633 nm). A notably higher SERS efficiency for CWA simulants was observed at a 325 nm Raman excitation. Our findings reveal that a higher ablation yield was observed at IR irradiation than those obtained at the other wavelengths. A size decrease of the NPs was noticed by changing the liquid environment to an electrolyte. These findings have significant implications for developing more efficient and stable SERS substrates for chemical detection applications.

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