Cholesterol drives enantiospecific effects of ibuprofen in biomimetic membranes.

The interaction between chiral drugs and biomimetic membranes is of interest in biophysical research and biotechnological applications. There is a belief that the membrane composition, particularly the presence of cholesterol, could play a pivotal role in determining enantiospecific effects of pharmaceuticals. Our study explores this topic focusing on the interaction of ibuprofen enantiomers (S- and R-IBP) with cholesterol-containing model membranes. The effects of S- and R-IBP at 20 mol% on bilayer mixtures of dipalmitoylphosphatidylcholine (DPPC) with 0, 10, 20 and 50 mol% cholesterol were investigated using circular dichroism and spin-label electron spin resonance. Morphological changes due to IBP enantiomers were studied with atomic force microscopy on supported cholesterol-containing DPPC monolayers. The results reveal that IBP isoforms significantly and equally interact with pure DPPC lipid assemblies. Cholesterol content, besides modifying the structure and the morphology of the membranes, triggers the drug enantioselectivity at 10 and 20 mol%, with the enantiomers differently adsorbing on membranes and perturbing them. The spectroscopic and the microscopic data indicate that IBP stereospecificity is markedly reduced at equimolar content of Chol mixed with DPPC. This study provides new insights into the role of cholesterol in modulating enantiospecific effects of IBP in lipid membranes.

Role of the Human Serum Albumin Protein Corona in the Antimicrobial and Photothermal Activity of Metallic Nanoparticles against Escherichia coli Bacteria.

The emergence of antibiotic-resistant bacteria has become a major public health concern, leading to growing interest in alternative antimicrobial agents. The antibacterial activity of metal nanoparticles (NPs) has been extensively studied, showing that they can effectively inhibit the growth of various bacteria, including both Gram-positive and -negative strains. The presence of a protein corona, formed by the adsorption of proteins onto the NP surface in biological fluids, can significantly affect their toxicity. Understanding the effect of the protein corona on the antimicrobial activity of metal NPs is crucial for their effective use as antimicrobial agents. In this study, the antimicrobial activity of noble metal NPs, such as platinum (Pt), silver (Ag), and gold (Au) with and without the human serum albumin (HSA) protein corona against Escherichia coli strains, was investigated. In addition, the plasmonic photothermal effect related to AuNPs, which resulted to be the most biocompatible compared to the other considered metals, was evaluated. The obtained results suggest that the HSA protein corona modulated the antimicrobial activity exerted by the metal NPs against E. coli bacteria. These findings may pave the way for the investigation and development of innovative nanoapproaches to face antibiotic resistance emergence.

Light-Induced Clusterization of Gold Nanoparticles: A New Photo-Triggered Antibacterial against E. coli Proliferation.

Metallic nanoparticles show plasmon resonance phenomena when irradiated with electromagnetic radiation of a suitable wavelength, whose value depends on their composition, size, and shape. The damping of the surface electron oscillation causes a release of heat, which causes a large increase in local temperature. Furthermore, this increase is enhanced when nanoparticle aggregation phenomena occur. Local temperature increase is extensively exploited in photothermal therapy, where light is used to induce cellular damage. To activate the plasmon in the visible range, we synthesized 50 nm diameter spherical gold nanoparticles (AuNP) coated with polyethylene glycol and administered them to an E. coli culture. The experiments were carried out, at different gold nanoparticle concentrations, in the dark and under irradiation. In both cases, the nanoparticles penetrated the bacterial wall, but a different toxic effect was observed; while in the dark we observed an inhibition of bacterial growth of 46%, at the same concentration, under irradiation, we observed a bactericidal effect (99% growth inhibition). Photothermal measurements and SEM observations allowed us to conclude that the extraordinary effect is due to the formation, at low concentrations, of a light-induced cluster of gold nanoparticles, which does not form in the absence of bacteria, leading us to the conclusion that the bacterium wall catalyzes the formation of these clusters which are ultimately responsible for the significant increase in the measured temperature and cause of the bactericidal effect. This photothermal effect is achieved by low-power irradiation and only in the presence of the pathogen: in its absence, the lack of gold nanoparticles clustering does not lead to any phototoxic effect. Therefore, it may represent a proof of concept of an innovative nanoscale pathogen responsive system against bacterial infections.

The interaction of tryptophan enantiomers with model membranes is modulated by polar head type and physical state of phospholipids.

The mutual influence of chiral bioactive molecules and supramolecular assemblies is currently being studied in many research fields, including medical-pharmaceutical applications. Model membranes of phospholipids, such as the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the anionic dipalmitoylphosphatidylglycerol (DPPG), interact with a variety of chiral compounds that include amino acids. In this work, the interaction of tryptophan enantiomers, L-Trp and D-Trp, on DPPC and DPPG bilayers was investigated by using differential scanning calorimetry, attenuated total reflectance-Fourier transform infrared and spin-label electron spin resonance spectroscopies as well as molecular docking simulations. The results show that Trp enantiomers slightly perturb the bilayer thermotropic phase transitions. For both membranes, O atoms in the carbonyl groups have a propensity to act as acceptors of a (weak) hydrogen bond. The Trp chiral forms also promote formation of hydrogen bonds and/or hydration in the PO2- moiety of the phosphate group, especially for the DPPC bilayer. In contrast, they interact more closely with the glycerol group of DPPG polar head. Only for DPPC bilayers, both enantiomers increase the packing of the first hydrocarbon chain segments for temperatures through the gel state, whereas they do not affect the lipid chain order and mobility in the fluid state. The results are consistent with a Trp association in the upper region of the bilayers without permeation in the innermost hydrophobic region. The findings suggest that neutral and anionic lipid bilayers are differently sensitive to amino acid chirality.

Chirality in Light-Matter Interaction.

The scientific effort to control the interaction between light and matter has grown exponentially in the last 2 decades. This growth has been aided by the development of scientific and technological tools enabling the manipulation of light at deeply sub-wavelength scales, unlocking a large variety of novel phenomena spanning traditionally distant research areas. Here, the role of chirality in light-matter interactions is reviewed by providing a broad overview of its properties, materials, and applications. A perspective on future developments is highlighted, including the growing role of machine learning in designing advanced chiroptical materials to enhance and control light-matter interactions across several scales.

All-Optical Tunability of Metalenses Permeated with Liquid Crystals.

Metasurfaces have been extensively engineered to produce a wide range of optical phenomena, allowing exceptional control over the propagation of light. However, they are generally designed as single-purpose devices without a modifiable postfabrication optical response, which can be a limitation to real-world applications. In this work, we report a nanostructured planar-fused silica metalens permeated with a nematic liquid crystal (NLC) and gold nanoparticle solution. The physical properties of embedded NLCs can be manipulated with the application of external stimuli, enabling reconfigurable optical metasurfaces. We report the all-optical, dynamic control of the metalens optical response resulting from thermoplasmonic-induced changes of the NLC solution associated with the nematic-isotropic phase transition. A continuous and reversible tuning of the metalens focal length is experimentally demonstrated, with a variation of 80 µm (0.16% of the 5 cm nominal focal length) along the optical axis. This is achieved without direct mechanical or electrical manipulation of the device. The reconfigurable properties are compared with corroborating numerical simulations of the focal length shift and exhibit close correspondence.

NIR-Absorbing Mesoporous Silica-Coated Copper Sulphide Nanostructures for Light-to-Thermal Energy Conversion.

Plasmonic nanostructures, featuring near infrared (NIR)-absorption, are rising as efficient nanosystems for in vitro photothermal (PT) studies and in vivo PT treatment of cancer diseases. Among the different materials, new plasmonic nanostructures based on Cu2-xS nanocrystals (NCs) are emerging as valuable alternatives to Au nanorods, nanostars and nanoshells, largely exploited as NIR absorbing nanoheaters. Even though Cu2-xS plasmonic properties are not linked to geometry, the role played by their size, shape and surface chemistry is expected to be fundamental for an efficient PT process. Here, Cu2-xS NCs coated with a hydrophilic mesoporous silica shell (MSS) are synthesized by solution-phase strategies, tuning the core geometry, MSS thickness and texture. Besides their loading capability, the silica shell has been widely reported to provide a more robust plasmonic core protection than organic molecular/polymeric coatings, and improved heat flow from the NC to the environment due to a reduced interfacial thermal resistance and direct electron-phonon coupling through the interface. Systematic structural and morphological analysis of the core-shell nanoparticles and an in-depth thermoplasmonic characterization by using a pump beam 808 nm laser, are carried out. The results suggest that large triangular nanoplates (NPLs) coated by a few tens of nanometers thick MSS, show good photostability under laser light irradiation and provide a temperature increase above 38 °C and a 20% PT efficiency upon short irradiation time (60 s) at 6 W/cm2 power density.

Biomimetic keratin gold nanoparticle-mediated in vitro photothermal therapy on glioblastoma multiforme.

Aim: To realize and characterize a new generation of keratin-coated gold nanoparticles (Ker-AuNPs) as highly efficient photosensitive nanosized therapeutics for plasmonic photothermal (PPT) therapy. Materials & methods: The chemical, physical, morphological and photothermal properties of Ker-AuNPs are investigated using dynamic light scattering, ζ-potential, UV-Visible, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, transmission electron microscopy and high-resolution thermography. In vitro experiments are performed on a human glioblastoma cell line (i.e., U87-MG), using viability assays, transmission electron microscopy, fluorescence microscopy, cytometric analyses and PPT experiments. Results: Experiments confirm the excellent biocompatibility of Ker-AuNPs, their efficient cellular uptake and localized photothermal heating capabilities. Conclusion: The reported structural and functional properties pointed out these Ker-AuNPs as a promising new tool in the field of biocompatible photothermal agents for PPT treatments against cancer-related diseases.

Thermo-Plasmonic Killing of Escherichia coli TG1 Bacteria.

Plasmonic photo-thermal therapy (PPTT) is a minimally invasive, drug-free, therapy based on the properties of noble metal nanoparticles, able to convert a bio-transparent electromagnetic radiation into heat. PPTT has been used against cancer and other diseases. Herein, we demonstrate an antimicrobial methodology based on the properties of gold nanorods (GNRs). Under a resonant laser irradiation GNRs become highly efficient light to heat nano-converters extremely useful for PPTT applications. The concept here is to assess the antimicrobial effect of easy to synthesize, suitably purified, water-dispersible GNRs on Escherichia coli bacteria. A control on the GNRs concentration used for the process has been demonstrated critical in order to rule out cytotoxic effects on the cells, and still to be able to generate, under a near infrared illumination, an adequate amount of heat suited to increase the temperature up to ≈50 °C in about 5 min. Viability experiments evidenced that the proposed system accomplished a killing efficiency suitable to reducing the Escherichia coli population of about 2 log CFU (colony-forming unit).

Antimicrobial Effects of Chemically Functionalized and/or Photo-Heated Nanoparticles.

Antibiotic resistance refers to when microorganisms survive and grow in the presence of specific antibiotics, a phenomenon mainly related to the indiscriminate widespread use and abuse of antibiotics. In this framework, thanks to the design and fabrication of original functional nanomaterials, nanotechnology offers a powerful weapon against several diseases such as cancer and pathogenic illness. Smart nanomaterials, such as metallic nanoparticles and semiconductor nanocrystals, enable the realization of novel drug-free medical therapies for fighting against antibiotic-resistant bacteria. In the light of the latest developments, we highlight the outstanding capabilities of several nanotechnology-inspired approaches to kill antibiotic-resistant bacteria. Chemically functionalized silver and titanium dioxide nanoparticles have been employed for their intrinsic toxicity, which enables them to exhibit an antimicrobial activity while, in a different approach, photo-thermal properties of metallic nanoparticles have been theoretically studied and experimentally tested against several temperature sensitive (mesophilic) bacteria. We also show that it is possible to combine a highly localized targeting with a plasmonic-based heating therapy by properly functionalizing nanoparticle surfaces with covalently linked antibodies. As a perspective, the utilization of properly engineered and chemically functionalized nanomaterials opens a new roads for realizing antibiotic free treatments against pathogens and related diseases.

Stereoselective and domain-specific effects of ibuprofen on the thermal stability of human serum albumin.

Ibuprofen is one of the most used anti-inflammatory drugs, and it is transported in the blood by human serum albumin, a major plasmatic protein with a peculiar adaptability in the binding of several different ligands. We have characterized the interaction between albumin and ibuprofen, either in racemic mixture, or in the S(+) and R(-) enantiomeric forms, by using differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, and molecular dynamics simulation. The results show that increasing concentrations of ibuprofen (up to sixfold drug/protein molar ratio) improve the protein resistance to thermal unfolding without altering the secondary structure. Deconvolution of the calorimetric thermal profiles at different albumin/ibuprofen molar ratios demonstrates a selective stability of the protein domains where the binding sites of the drug are localized. At the highest ibuprofen concentration, the melting temperature increased by about 10°C with respect to the drug-free protein, whereas the unfolding enthalpy maintains an almost constant value. Furthermore, the degree of protein stabilization depends upon the chirality of the drug, and the R(-) enantiomer is more effective compared to the S(+) form. The stability is supported by molecular dynamics simulations, showing that ibuprofen maintains a stable coordination in the most favorable binding sites, leading to a more compact protein structure at high temperature. The overall results attest that the binding of ibuprofen determines on albumin a stereoselective and domain-specific stabilization with a predominantly entropic character, contributing to clarify significant aspects of the molecular mechanism of protein/drug interaction.