Upgrading the Toolbox: Two-Photon Absorption Induced Cleavage of Coumarin Dimers for Light-Based 4D Printing.

The use of light for shaping and changing matter is of high relevance in polymer and material science. Herein, a photopolymer method is presented, which comprises the combination of 3D photo-printing at 405 nm light and subsequent modification under two-photon absorption (TPA) conditions at 532 nm light, adding the fourth dimension. The TPA-triggered cycloreversion reaction of an intramolecular coumarin dimer (ICD) structure occurs within the absorbing material. The 3D-printable matrix does not show any degradation under the TPA conditions. With the presented photochemical tool of TPA processes inside absorbing 3D photo-printable matrices, new possibilities for post-printing modification, e. g. for smart materials, are added.

The development of rare-earth combined Fe-based magnetic nanocomposites for use in biological theranostics.

Iron (Fe)-based nanoparticles (NPs) represented by Fe3O4 exhibit attractive properties, such as high saturation magnetization, low magneto-crystalline anisotropy, and good biocompatibility, and are useful as magnetic resonance imaging (MRI) contrast agents. However, the existence of artifacts makes the single magnetic resonance imaging mode lack accuracy in tumor diagnosis. To overcome this limitation, a strategy where rare-earth elements are combined with Fe-based NPs is applied. Rare earth is the general name of Sc, Y, and elements with unique 4f electronic configurations. Some rare-earth elements like Gd and Lu exhibit magnetic properties due to unpaired electrons, while some, like Er and Ho, fluoresce under excitation ascribed to the electron transition at intermediate energy levels. In this manuscript, attention is focused on multimodal nanomaterials composed of rare-earth elements and Fe-based NPs. We provide an overview of the synthetic routes and current biomedical application of the nanocomposites that show potential for precise diagnosis and efficient treatment of cancers.

Laser-Induced Au Catalyst Generation for Tailored ZnO Nanostructure Growth.

ZnO nanostructures, semiconductors with attractive optical properties, are typically grown by thermal chemical vapor deposition for optimal growth control. Their growth is well investigated, but commonly results in the entire substrate being covered with identical ZnO nanostructures. At best a limited, binary growth control is achieved with masks or lithographic processes. We demonstrate nanosecond laser-induced Au catalyst generation on Si(100) wafers, resulting in controlled ZnO nanostructure growth. Scanning electron and atomic force microscopy measurements reveal the laser pulse's influence on the substrate's and catalyst's properties, e.g., nanoparticle size and distribution. The laser-induced formation of a thin SiO2-layer on the catalysts plays a key role in the subsequent ZnO growth mechanism. By tuning the irradiation parameters, the width, density, and morphology of ZnO nanostructures, i.e., nanorods, nanowires, and nanobelts, were controlled. Our method allows for maskless ZnO nanostructure designs locally controlled on Si-wafers.

Laser-Driven One- and Two-Dimensional Subwavelength Periodic Patterning of Thin Films Made of a Metal-Organic MoS2 Precursor.

Laser-based surface processing is an established way for the maskless generation of surface structures and functionalities on a large variety of materials. Laser-driven periodic surface texturing and structuring of thin films is reported for metallic-, semiconductive-, and polymeric films. Here, we introduce subwavelength surface patterning of metal-organic thin films of [Mo2S4(S2CNnBu2)2], a MoS2 precursor. Accurate control of one- and two-dimensional (1D and 2D) periodic patterns is achieved on silicon wafers with a pulsed 532 nm ns laser. With suitable combinations of laser polarization, laser pulse energy, the thickness of the SiO2 passivation layer, and the MoS2 precursor's thin film thickness, high-quality 1D and 2D self-organized periodic structures are obtained in virtually unlimited areas. The material redistribution related to the pattern formation is thermally driven at low laser energies. Increasing pulse energies beyond a threshold level, in our experiments a factor of 2, fully converts the precursor to MoS2.

An intelligent tumor microenvironment responsive nanotheranostic agent for T1/T2 dual-modal magnetic resonance imaging-guided and self-augmented photothermal therapy.

Photothermal therapy (PTT), as a promising antineoplastic therapeutic strategy, has been harnessed to restrain tumor growth through near-infrared (NIR) irradiation mediated thermal ablation. Nevertheless, its biological applications are hampered by thermal diffusion and up-regulated heat shock proteins (HSPs). Herein, a versatile nanotheranostic agent is developed via integrating Zn0.2Fe2.8O4 nanoparticles (NPs), polydopamine (PDA), and MnO2 NPs for T1/T2 dual-modal magnetic resonance (MR) imaging-guided and self-augmented PTT. The as-designed Zn0.2Fe2.8O4@PDA@MnO2 NPs adequately serve as a PTT agent to realize effective photothermal conversion and obtain local hyperthermia. Additionally, the Zn0.2Fe2.8O4@PDA@MnO2 NPs can significantly consume overexpressed glutathione (GSH) and generate Mn2+ in the tumor microenvironment (TME), thus destroying redox homeostasis and catalytically generating hydroxyl radicals (˙OH) for HSP suppression and PTT enhancement. Meanwhile, Mn2+ and Zn0.2Fe2.8O4 NPs significantly strengthen T1- and T2-weighted MR contrast for tumor imaging and PTT guidance. Hence, this study offers proof of concept for self-augmented PTT and T1/T2 dual-modal MR imaging for tumor elimination.

Cycloreversion performance of coumarin and hetero-coumarin dimers under aerobic conditions: unexpected behavior triggered by UV-A light.

Photochemical [2+2]-cycloadditions of coumarin-like monomers are the textbook paradigms of photo-formation and photo-cleavage reactions. The electronic conjugation length of monomers and dimers is quite different which results in almost fully separated UV/Vis absorption bands in the UV-A and UV-C. This feature enables the selective light-controlled conversion between monomeric and dimeric forms by the choice of the appropriate wavelengths. Several applications are based on this kind of reversible photo linker without absorption in the visible range. But which is the best molecule from the coumarin family for such an application? Within this study, we compared the photochemical cleavage behavior of twelve coumarin-type cyclobutane dimers. In particular, the influence of isomer structure and substitution pattern was studied. Two dimers with an unexpected high quantum yield for cyclobutane cleavage were identified. This behavior is explained through the differing ring strain of the cyclobutane moiety. Electron donating substitutions of the framework, e.g. with a methoxy function (+M-effect), leads to a decreased oxidation potential, making the dimers sensitive towards oxidative dimer splitting. This result disqualifies coumarins, e.g. attached to a polymer backbone via an ether bond, often in the 7-position, because of their instabilities and side reactions in an aerobic environment. The methylated dimers (+I-effect) show excellent stability towards this undesired side reaction as well as a high cleavage efficiency upon irradiation with 265 nm. All twelve investigated dimers are ranked for their quantum efficiency and rate constant for cleavage at 265 nm, as well as their oxygen tolerance. As the most promising derivative within our scope for applications the methylated coumarin dimer was identified.

Oxidative formation of bis-N-methylquinolinone from anti-head-to-head N-methylquinolinone cyclodimer.

The light-driven formation and cleavage of cyclobutane structural motifs resulting from [2 + 2]-pericyclic reactions, as found in thymine and coumarin-type systems, is an important and intensively studied photochemical reaction. Various applications are reported utilizing these systems, among others, in cross-linked polymers, light-triggered drug release, or other technical applications. Herein coumarin is most frequently used as the photoactive group. Quite often, a poor quantum yield for dimerization and cyclobutane-cleavage and a lack of reversibility are described. In this work, we present the identification of a heterogeneous pathway of dimer cleavage found in a rarely studied coumarin analog molecule, the N-methyl-quinolinone (NMQ). The monomer was irradiated in a tube flow-reactor and the reaction process was monitored using online HPLC measurements. We found the formation of a pseudo-equilibrium between monomeric and dimeric NMQ and a continuous rise of a side product via oxidative dimer splitting and proton elimination which was identified as 3,3'-bis-NMQ. Oxidative conversion by singlet oxygen was identified to be the cause of this non-conventional cyclobutane cleavage. The addition of antioxidants suppressing singlet oxygen enables achieving a 100% photochemical conversion from NMQ to the anti-head-to-head-NMQ-dimer. Using dissolved oxygen upon light activation to singlet oxygen limits the reversibility of the photochemical [2 + 2]-cycloaddition and cycloreversion of NMQ and most likely comparable systems. Based on these findings, the development of highly efficient cycloaddition-cycloreversion systems should be enabled.

Fusion of purple membranes triggered by immobilization on carbon nanomembranes.

A freestanding ultrathin hybrid membrane was synthesized comprising two functional layers, that is, first, a carbon nanomembrane (CNM) produced by electron irradiation-induced cross-linking of a self-assembled monolayer (SAM) of 4'-nitro-1,1'-biphenyl-4-thiol (NBPT) and second, purple membrane (PM) containing genetically modified bacteriorhodopsin (BR) carrying a C-terminal His-tag. The NBPT-CNM was further modified to carry nitrilotriacetic acid (NTA) terminal groups for the interaction with the His-tagged PMs forming a quasi-monolayer of His-tagged PM on top of the CNM-NTA. The formation of the Ni-NTA/His-tag complex leads to the unidirectional orientation of PM on the CNM substrate. Electrophoretic sedimentation was employed to optimize the surface coverage and to close gaps between the PM patches. This procedure for the immobilization of oriented dense PM facilitates the spontaneous fusion of individual PM patches, forming larger membrane areas. This is, to our knowledge, the very first procedure described to induce the oriented fusion of PM on a solid support. The resulting hybrid membrane has a potential application as a light-driven two-dimensional proton-pumping membrane, for instance, for light-driven seawater desalination as envisioned soon after the discovery of PM.

Assembling Carbon Nanotube Architectures.

Well-defined multiwalled carbon nanotube structures are generated on stainless steel AISI 304 (EN AW 1.4301) by chemical vapor deposition. Pulsed laser-induced dewetting (PLiD) of the surface, by 532 nm nanosecond laser pulses, is utilized for the preparation of metal oxide nanoparticle fields with a defined particle number per area. The reduction of the precursor particles is achieved in an Ar/H2 (10% H2) atmosphere at 750 °C, thereby generating catalytic nanoparticles (c-NPs) for carbon nanotube (CNT) growth. Ethylene is used as a precursor gas for CNT growth. CNT lengths and morphology are directly related to the c-NP aerial density, which is dependent on the number of dewetting cycles during the PLiD process. Within a narrow window of c-NP per area, vertically aligned carbon nanotubes of great lengths are obtained. For more intense laser treatments, three-dimensional dewetting occurs and results in the formation of cauliflower-like structures. The laser process enables the creation of all kinds of CNT morphologies nearby on the microscale.

Effect of elasticity on the phagocytosis of micro/nanoparticles.

A broad range of investigation methods and frameworks are currently used to throughly study the elasticity of various types of micro/nanoparticles (MNPs) with different properties and to explore the effect of such properties on their interactions with biological species. Specifically, the elasticity of MNPs serves as a key influencing factor with respect to important aspects of phagocytosis, such as the clathrin-mediated phagocytosis, caveolae-mediated phagocytosis, macropinocytosis, and cell membrane fusion. Achieving a clear understanding of the relationships that exist between the elasticity of MNPs and their phagocytic processes is essential to improve their performance in drug delivery, which is related to aspects such as circulation lifetime in blood, accumulation time in tissues, and resistance to metabolism. Resolving such aspects is very challenging, and related efforts require using the right tools/methods, which are not always easy to identify. This review aims to facilitate this by summarizing and comparing different cell phagocytosis pathways, while considering various MNPs exhibiting different elastic properties, shape change capabilities, and their effect on cellular uptake. We conduct an overview of the advantages exhibited by different MNPs with respect to both in vitro and in vivo delivery, taking computational simulation analysis and experimental results into account. This study will provide a guide for how to investigate various types of MNPs in terms of their elastic properties, together with their biomedical effects that rely on phagocytosis.

The role of phosphopeptides in the mineralisation of silica.

We investigated the silicification activity of hyperphosphorylated peptides in combination with long-chain polyamines (LCPA). The bioinspired in vitro silicification experiments with peptides containing different amounts of phosphorylated serines showed structure-activity dependence by altering the amount and morphology of the silica precipitate. Our study provides an explanation for the considerable metabolic role of diatoms in the synthesis of hyperphosphorylated poly-cationic peptides such as natSil-1A1. The efficient late-stage phosphorylation of peptides yielded a synthetic heptaphosphopeptide whose silicification properties resemble those of natSil-1A1. As opposed to this, unphosphorylated poly-cationic peptides or LCPA require concentrations above 1 mM for silicification. Hyperphosphorylated peptides showed a linear dependence between the amount of dissolved peptides and the amount of precipitated silica in the concentration range below 1 mM. Under mildly acidic conditions and short precipitation times, the concentration of the added LCPA determined the size of the silica spheres.

Synthesis of gold-silica core-shell nanoparticles by pulsed laser ablation in liquid and their physico-chemical properties towards photothermal cancer therapy.

Due to the increasing scientific and biomedical interest in various nanoparticles (NPs) with excellent properties and the onset of their commercial use, a convenient and adjustable physical method for improved efficiency needs to be used for enabling their tech-scale production. Recently, great progress has been made in the large-scale production of NPs with a simple structure by pulsed laser ablation in liquid (PLAL). In this work, we synthesized gold-silica core-shell NPs by improved PLAL and provided a guide on how to investigate their physico-chemical properties and association with biological effects towards cancer photothermal therapy (PTT). By means of this method, reproducible and scalable liquid phase NPs with less toxicity and good stability can be realized for tech-scale production based on its further adjustment and modification. Moreover, a more complete investigation of the associations between the physico-chemical properties of functional NPs with complex structure and their biological effects may enable more targeted NPs towards specific requirements of biomedical applications.

Formation of Highly Ordered Platinum Nanowire Arrays on Silicon via Laser-Induced Self-Organization.

Laser-induced periodic surface structures (LIPSS) provide an elegant solution for the generation of highly ordered periodic patterns on the surface of solids. In this study, LIPSS are utilized for the formation of periodic platinum nanowire arrays. In a process based on laser-stimulated self-organization, platinum thin films, sputter-deposited onto silicon, are transformed into nanowire arrays with an average periodicity of 538 nm. The width of the platinum nanowires is adjustable in a range from 20 nm to 250 nm by simply adjusting the thickness of the initial platinum thin films in a range from 0.3 nm to 4.3 nm. With increasing width, platinum nanowires show a rising tendency to sink into the surface of the silicon wafer, thus indicating alloying between platinum and silicon upon LIPSS-formation by a nanosecond-pulsed laser. The Pt/silicon wires may be etched away, leaving a complementary nanostructure in the silicon surface.

Applications of magnetic materials separation in biological nanomedicine.

As a result of their advantages for superparamagnetic properties, good biocompatibility, and high binding capacity, functionalized magnetic materials became widely popular over the past couple of decades, being applied on large scale in various processes of sample preparation for biomedicine. In this work, we perform an in-depth review on the current progress in the field of magnetic bead separation, discussing in detail the physical basis of this process, various synthesis methods and surface modification strategies. We place special focus of attention as well on the latest applications of magnetic polymer microspheres in cell separation, protein purification, immobilized enzyme, nucleic acid separation, and extraction of bioactive compounds with low molecular weight. Existing problems are highlighted and possible trends of magnetic separation techniques for biomedicine in the future are proposed.

Reactive metal-organic interfaces studied with hard x-ray photoelectron spectroscopy: controlled formation of metalloporphyrin interphase layers during metal vapor deposition onto porphyrin films.

Interfaces between organic semiconductors and metallic layers are ubiquitous in organic (opto-) electronic devices and can significantly influence their functionality. Here, we studied in situ prepared metal-organic interfaces, which were obtained by vapor deposition of metals (Co, Fe) onto organic semiconductor films (2H-tetraphenylporphyrin), with hard x-ray photoelectron spectroscopy. In these systems, the interphase zones, which are formed by diffusion and reaction of the metal in the organic material, can be clearly distinguished spectroscopically from the unreacted organic bulk, since they comprise the corresponding metalloporphyrins, CoTPP and FeTPP. In order to gain control over the thickness of the interphase layers, we varied process parameters such as sample temperature and metal-atom flux during interface preparation. We found that the temperature of the organic film during metal deposition was the only parameter that significantly influenced the formation of the interphase layers: their thicknesses were typically ~0.5 nm for deposition at 90 K, compared to ~1 nm at 300 K, irrespective of metal atom flux and chemical nature of the metal atom (Fe versus Co). Notably, these values are significantly smaller than the thicknesses of other metal/organics interphase regions reported in the literature.

Substituting Coumarins for Quinolinones: Altering the Cycloreversion Potential Energy Landscape.

The light-activated cleavage of cyclobutane-based systems via [2 + 2] cycloreversions, such as thymine and coumarin dimers, is an important but still poorly understood ultrafast photochemical reaction. Systems displaying reversible cycloreversion have found various uses in cross-linked polymers, enhancing gas adsorption affinities in inorganics, and light-activated medical therapies. We report the identification of a heterogeneous mode of cycloreversion for a rarely examined coumarin analogue system. Quinolinone monomers and dimers were probed using ultraviolet pumped, transient absorption spectroscopy and demonstrated radically different photophysical properties than coumarins. Monomers displayed enhanced intersystem crossing at almost 1:1 versus the combined nonradiative and radiative singlet decay, while the dimers underwent cycloreversion to a one excited-one ground state monomer photoproduct pair. The change in both systems was directly linked to the lactame group in the quinolinone motif. This discovery highlights the dramatic effects that small chemical changes can have on photoreaction pathways and opens up a new means to produce and develop more efficient cycloaddition-cycloreversion systems.

Mechanically metastable structures generated by single pulse laser-induced periodic surface structures (LIPSS) in the photoresist SU8.

Laser-induced periodic surface structures (LIPSS) with a periodicity of 351 nm are generated in the negative photoresist SU8 by single nanosecond laser pulse impact. Friction scans indicate the periodic pattern to comprise alternating regions of crosslinked and non-crosslinked SU8. Intriguingly, even minor mechanical stimuli in the order of nanonewtons cause the unfolding or rather the deletion of the characteristic periodic pattern similarly to the release of a pre-loaded spring. This feature combined with high resilience to heat and photon irradiation makes SU8-LIPSS attractive for applications such as mechanical stress monitors, self-destructing memory and passive micro actuators.

Investigations on the elasticity of functional gold nanoparticles using single-molecule force spectroscopy.

A wide range of investigation tools and frameworks aimed at the in depth understanding of the physico-chemical properties of different nanomaterials and at exploring their cellular interactions and effects have been reported in the past couple of decades. Among these, Single-Molecule Force Spectroscopy (SMFS) emerges as a very important tool for characterizing nanoparticles (NPs) and one of its very valuable applications consists in the quantitative analysis of the NPs' elasticity. In SMFS experiments that tackle this subject, a sharp tip present on the apex of a cantilever is indented into a single NP, and then the Young's modulus is determined as a measure of its elasticity, which is one of the fundamental mechanical parameters affecting the structural and functional cellular parameters. Based on such approaches, SMFS enables the observation and analysis of significant cellular effects that are relevant to various cellular parameters. In this focused review, we turn our attention towards several approaches for detecting the elasticity of NPs, systematically summarizing the divergent elasticity values of distinct gold nanoparticles (AuNPs) with different surfaces. We carry as well a critical discussion on the elasticity assessment models and the fundamental factors that influence NP elasticity assessment by means of SMFS.

Colloidal Gold Nanoparticles Induce Changes in Cellular and Subcellular Morphology.

Exposure of cells to colloidal nanoparticles (NPs) can have concentration-dependent harmful effects. Mostly, such effects are monitored with biochemical assays or probes from molecular biology, i.e., viability assays, gene expression profiles, etc., neglecting that the presence of NPs can also drastically affect cellular morphology. In the case of polymer-coated Au NPs, we demonstrate that upon NP internalization, cells undergo lysosomal swelling, alterations in mitochondrial morphology, disturbances in actin and tubulin cytoskeleton and associated signaling, and reduction of focal adhesion contact area and number of filopodia. Appropriate imaging and data treatment techniques allow for quantitative analyses of these concentration-dependent changes. Abnormalities in morphology occur at similar (or even lower) NP concentrations as the onset of reduced cellular viability. Cellular morphology is thus an important quantitative indicator to verify harmful effects of NPs to cells, without requiring biochemical assays, but relying on appropriate staining and imaging techniques.

Diverse Applications of Nanomedicine.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.