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Proton therapy is used to eradicate tumors in sensitive areas by targeted delivery of energy. Its effectiveness can be amplified using nanoparticles (NPs) as sensitizers, due to the production of reactive oxygen species at the NP's catalytically active surface, causing the cleavage of DNA. However, the impact of stabilizing macromolecular ligands capping the particles, needed for nanosensitizer dispersion in physiological fluids, is underexplored. Herein, ligand‐free colloidal platinum NPs (PtNPs) fabricated by scalable laser synthesis in liquids are used, which allows studying particle and ligand effects separately. PtNPs are incubated with stabilizing concentrations of the clinically approved ligands albumin, Tween, and polyethylene glycol, and irradiated with proton beams at clinically relevant doses (2 and 5 Gy). At these doses, plasmid DNA cleavage larger than 55% of clustered DNA damage is achieved. Bovine serum albumin, Tween, and polyethylene glycol on the NP surface work as double‐strand breaks (DSB) enhancers and synergetic effects occur even at low and clinically relevant particle concentrations and irradiation doses. Here, DSB enhancement by ligand‐capped PtNP even exceeds the sum of the individual ligand and particle effects. The presented fundamental correlations provide selection rules for nanosensitizer design in proton therapy. [ABSTRACT FROM AUTHOR]

Among various hybrid nanomaterials, the combination of plasmonic nanoparticles and fluorophores in a single multifunctional nanoplatform, so‐called plasmophores, has attracted significant attention in different fields such as dark field, fluorescence, and photoacoustic imaging, biosensing, photothermal, and photodynamic therapy. Herein, author report a facile and controlled synthesis route of hybrid nanoplatforms composed of fluorescent gold nanoclusters (GNCs) coupled to plasmonic gold nanorods (GNRs) using controlled silica (SiO2) dielectric spacers of different thicknesses from now on referred to as GNR@SiO2@GNC plasmophores. The results show different degrees of plasmon‐enhanced fluorescence of the GNCs in their plasmophore hybrid system when placed at different distances from the plasmonic cores of the GNRs. On the other hand, these plasmophores show enhanced thermal stability compared to GNRs@CTAB (CTAB, cetyl trimethyl ammonium bromide). This results also demonstrated that upon annealing at elevated temperatures (800–1000 °C), the GNRs in the plasmophores are more thermally stable and robust than the GNRs@CTAB. More surprisingly, despite the commonly reported very low melting temperature of smaller‐size nanocrystals, the GNCs in the plasmophores showed high thermal stability and do not exhibit significant structural changes at elevated temperatures (800–1000 °C). [ABSTRACT FROM AUTHOR]

The rising number of antibiotic‐resistant bacteria requires alternative antibacterial substances as therapeutics. However, besides a strong effect against bacteria, they should not exhibit cytotoxicity towards human cells. Typically, both properties are tested in separate in vitro experiments that do not take into account naturally occurring interactions. To analyze whether the bacteria‐cell interaction influences the results of antibacterial and cytotoxic testing, surfactant‐free antibacterial silver‐gold alloy nanoparticles produced by laser ablation in liquid were examined both separately and in a straightforward coculture setup. Whereas different commensal bacteria and human skin cells exhibited reduced metabolic activity at comparable concentrations when treated separately, their response completely differed when analyzed in a combined coculture. For the combination of oral keratinocytes and Staphylococcus aureus, reduced cytotoxicity with increasing cell numbers, but a similar antibacterial effect quantified by standard plate counting could be observed. In contrast, coculture of keratinocytes and Porphyromonas gingivalis resulted in a complete absence of cytotoxicity and antibacterial effect, probably due to bacterial invasion of cells. These results clearly showed that the bacteria‐cell interaction greatly influences the results of antibacterial and cytotoxic testing and highlight the importance of more complex in vitro experiments to reliably characterize novel antibacterial substances for efficient clinical translation. [ABSTRACT FROM AUTHOR]

One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). Moreover, the underlying predominantly photo‐mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are currently the most studied radiosensitizers in proton therapy (PT) applicable for the treatment of solid tumors, where they amplify production of reactive oxygen species (ROS). However, it is underexplored how this amplification is correlated with the AuNPs' surface chemistry. To clarify this issue, we fabricated ligand‐free AuNPs of different mean diameters by laser ablation in liquids (LAL) and laser fragmentation in liquids (LFL) and irradiated them with clinically relevant proton fields by using water phantoms. ROS generation was monitored by the fluorescent dye 7‐OH‐coumarin. Our findings reveal an enhancement of ROS production driven by I) increased total particle surface area, II) utilization of ligand‐free AuNPs avoiding sodium citrate as a radical quencher ligands, and III) a higher density of structural defects generated by LFL synthesis, indicated by surface charge density. Based on these findings it may be concluded that the surface chemistry is a major and underexplored contributor to ROS generation and sensitizing effects of AuNPs in PT. We further highlight the applicability of AuNPs in vitro in human medulloblastoma cells. [ABSTRACT FROM AUTHOR]

Bioactive glass (BG) is a frequently used biomaterial applicable in bone tissue engineering and known to be particularly effective when applied in nanoscopic dimensions. In this work, we employed the scalable reactive laser fragmentation in liquids method to produce nanosized 45S5 BG in the presence of light‐absorbing Fe and Cu ions. Here, the function of the ions was twofold: (i) increasing the light absorption and thus causing a significant increase in laser fragmentation efficiency by a factor of 100 and (ii) doping the BG with bioactive metal ions up to 4 wt%. Our findings reveal an effective downsizing of the BG from micrometer‐sized educts into nanoparticles having average diameters of <50 nm. This goes along with successful element‐specific incorporation of the metal ions into the BG, inducing co‐doping of Fe and Cu ions as verified by energy‐dispersive X‐ray spectroscopy (EDX). In this context, the overall amorphous structure is retained, as evidenced by X‐ray powder diffraction (XRD). We further demonstrate that the level of doping for both elements can be adjusted by changing the BG/ion concentration ratio during laser fragmentation. Consecutive ion release experiments using inductively‐coupled plasma mass spectrometry (ICP‐MS) were conducted to assess the potential bioactivity of the doped nanoscopic BG samples, and cell culture experiments using MG‐63 osteoblast‐like cells demonstrated their cytocompatibility. The elegant method of in situ co‐doping of Fe and Cu ions during BG nanosizing may provide functionality‐advanced biomaterials for future studies on angiogenesis or bone regeneration, particularly as the level of doping may be adjusted by ion concentrations and ion type in solution. [ABSTRACT FROM AUTHOR]

Stent therapy can reduce both morbidity and mortality of chronic coronary stenosis and acute myocardial infarction. However, delayed re‐endothelialization, endothelial dysfunction, and chronic inflammation are still unsolved problems. Alginate hydrogels can be used as a coating for stent surfaces; however, complete and fast endothelialization cannot be achieved. In this study, alginate hydrogels are modified by fibrin blending, iron nanoparticle (Fe‐NP) embedding, and serum protein coating (SPC) while surface properties and endothelialization capacity are monitored. Only a triple, synergetic modification of the alginate coating by simultaneous I) fibrin blending, II) Fe‐NP addition complemented by III) SPC is found to significantly improve endothelial cell viability (live–dead‐staining) and proliferation (WST‐8 assay). These conditions yield formation of closed endothelial cell monolayers and an up to threefold increase (p < 0.01) in viability, while, interestingly, no effect is found when the modifications (I)–(III) are conducted individually. This synergetic effect is attributed to an accumulation of agglomerated Fe‐NP and serum proteins along fibrin fibers, observed via laser scanning microscopy tracking nanoparticle scattering and tetramethylrhodamine (TRITC)‐albumin fluorescence. These synergetic effects can pave the way toward a novel strategy for the modification of various hydrogel‐based biomaterials and biomaterial coatings. [ABSTRACT FROM AUTHOR]