Molecular photoswitches capable of controlling membrane properties under light stimulation represent promising tools for manipulating biomimetic and biological interfaces. We report the synthesis and photophysical characterization of amphiphilic P-type photoswitches exhibiting efficient and reversible E↔Z photoisomerization under both one-photon (1PA: 375/300 nm) and two-photon (2PA: 750/630 nm) excitation. Their incorporation into DPPC monolayers and bilayers enables light-driven modulation of membrane structure. Short-chain analogues (C4 derivatives) remain well-mixed with DPPC and promote curvature upon E↔Z photoisomerization, regardless of the polarity of their headgroup (hydroxyl, OH, or hexaethylenglycol, HEG). In contrast, long-chain derivatives (C12) behave either as light-activated compressants or expanders depending on the strength of their headgroup interactions. The HEG-terminated C12 photoswitch (Sw-HEG-C12) favors anchoring at the interface and induces lateral demixing (microsegregation) and domain stiffening, leading to a decrease in surface pressure in DPPC monolayers and an increase in vesicle size upon E→Z isomerization. Conversely, the hydroxylated analogue (Sw-OH-C12) mixes nearly ideally with DPPC but occupies different depths within the bilayer depending on isomerization state (E near the interface, Z internalized), resulting in an increase in surface pressure and a decrease in vesicle size upon E→Z isomerization. The two-photon-responsive photoswitches reported herein appear thus as versatile tools for the optical control of membrane architecture in biological environments where NIR light is required.

Temperature measurements at the nanoscale are essential for understanding physiological and pathological processes. Here, we report fluorescent polymeric nanothermometers (FPTSs) based on thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) endfunctionalized with environment-sensitive DCM-like fluorophores, which self-assemble into well-defined nanoparticles in aqueous media. Two closely related probes, DCMC and DCMQ, exhibiting similar solvatochromic behavior but opposite aggregation tendencies (aggregation-caused quenching, ACQ, vs aggregation-induced emission, AIE), are used to screen the respective contributions of aggregation, polarity, and microviscosity in the temperature-dependent fluorescence response. Upon heating, the LCST-driven collapse of PNIPAM triggers nanoscale reorganization of the polymeric assemblies, leading to a local environment of reduced polarity and increased microviscosity. This results in a fluorescence enhancement accompanied by a spectral blue shift, enabling both intensityand ratiometric-based temperature sensing. The systems display high sensitivity, including in the physiological temperature range. In particular, the DCMC-based nanothermometer combines a large Stokes shift with near-infrared emission, highlighting its potential for bioimaging applications.

Photothermal therapy (PTT) offers a minimally invasive approach for treating hypoxic tumors, while photodynamic therapy (PDT) is limited by its oxygen dependence. Indocyanine green (ICG) is a clinically approved near-infrared (NIR) dye with potential for PTT and PDT, but its application is hindered by poor photostability, rapid clearance, and aggregation, resulting in unfavorable pharmacokinetics and limited phototherapeutic performances. Here, we address these limitations through a combination of chemical transformation of ICG by dimerization, controlled supramolecular assembly into dye aggregates, and a tailored formulation strategy. We systematically compared three forms, monomeric ICG, its covalent dimer (dICG), and the corresponding J-aggregate (dIJA), each formulated into polyion complex nanoparticles (PNPs) using poly(2-ethyl-2-oxazoline)-b-poly(L-ornithine) as the polyelectrolyte carrier matrix. Subsequent genipin-mediated core crosslinking produced crosslinked nanoparticles (CPNPs) with enhanced stability, high encapsulation efficiency, and preserved optical characteristics. CPNPs consistently outperformed free dye and non-crosslinked PNPs, showing improved colloidal stability, enhanced photostability, and higher photothermal performances. In FaDu cells, ICG-loaded CPNPs mediated oxygen-dependent photodynamic effects, whereas dICG- and dIJA-loaded CPNPs induced oxygen-independent photothermal cytotoxicity under NIR irradiation. Our integrated comparison demonstrates that controlling the molecular form and supramolecular assembly of ICG derivatives enables tunable NIR phototherapy, identifying dICG- and dIJA-based CPNPs as promising platforms for the treatment of hypoxic tumors by photoacoustic imaging (PAI) guided PTT.

Background: Antimicrobial resistance (AMR) represents a critical global health challenge, requiring innovative strategies to combat resistant bacterial strains. Cymbopogon essential oils (EOs) are promising natural antimicrobial agents. Methods: The EO of Cymbopogon commutatus was extracted by hydrodistillation from fresh aerial parts and compared to commercial EOs from C. citratus, C. nardus, and C. winterianus. Antibacterial activity was evaluated against seven bacterial strains (two Gram-positive and five Gram-negative). Both water-soluble fractions and liposome-encapsulated formulations were tested. Liposomes were prepared using soybean lecithin, and their stability was assessed by dynamic light scattering (DLS). The chemical composition of the pure EOs, water-soluble fractions and non-water-soluble fractions was analyzed by gas chromatography–mass spectrometry (GC-MS). Results: Liposome encapsulation improved EO solubility in aqueous media and significantly enhanced antibacterial efficacy, reducing minimum inhibitory concentration (MIC) values compared to the water-soluble fractions (MICs ≥ 25%). Among the tested formulations, the liposome containing C. citratus EO exhibited the strongest inhibitory effect against Staphylococcus aureus (MIC: 0.04%) followed by liposomes with C. nardus and C. commutatus (MIC: 0.08%). Against Enterococcus faecalis, the most effective formulation was the liposome containing C. winterianus EO (MIC: 0.02%), followed by C. citratus (MIC: 0.08%). The liposome formulated with C. winterianus maintained its particle size over 72 h without phase separation. GC-MS analysis revealed distinct phytochemical profiles: C. commutatus EO was rich in piperitone (73.9%) and C. citratus was rich in (Z)-(3,3-Dimethyl)-cyclohexylideneacetaldehyde (39.9%) and citral (32.5%), while C. nardus and C. winterianus were dominated by geraniol (21.5%) and citronellal (30.8%), respectively. Notably, piperitone, the major compound in C. commutatus EO, exhibited strong antibacterial activity against S. aureus (MIC of <0.04%). Conclusions: These findings support the potential of liposome-encapsulated Cymbopogon EOs as an effective and sustainable strategy to address AMR. This study provides a foundation for the development of plant-based antimicrobial formulations with improved efficacy.

The control of the activation of the innate immune response, notably by using suitable visible light sources, may lead the way to the development of phototimmunotherapeutic strategies. In this contribution we analyze the effects of the E/Z interconversion on a phosphatidyl serine lipid containing an isomerizable azobenzene moiety, which has recently been shown to regulate the activation of natural killer cells and the production of cytokines [J. Am. Chem. Soc. 2022, 144, 3863 - 3874]. In particular, we analyze the differential interactions of the innate immune system TIM-3 sensors. We show, resorting to long-range molecular dynamic simulations including enhanced sampling, that the Z isomer leads to a slight decrease of the binding free energy coupled with a less pronounced rigidification of the protein compared to the E isomer and the native lipid, justifying its less pronounced activation of the immune response.

To make pyrolytic bio‐oil useful as a transportation fuel, the oxygen content must be reduced, and this can be carried out by using catalytic hydrodeoxygenation (HDO) reaction. The greatest challenge is associated with the removal of strongly bound oxygenated groups without saturating the aromatic ring while preserving the number of carbons. However, the development of a stable catalyst that can selectively remove such oxygenated groups with low hydrogen consumption is still challenging. In this context, a systematic study on HDO of vanillin on bimetallic Pd‐Pt catalysts was carried out. It aims to study the effect of bimetallic synergy in terms of activity and selectivity to creosol. Metallic nanoparticles of Pd and Pt were synthesized by sol immobilization technique and deposited on TiO2. The conversion of vanillin was correlated to the Pd‐Pt atomic ratio, while the production of the creosol was correlated to the Pd(0)/(Pd+Pt) ratio at the surface. Full conversion of vanillin was obtained at low reaction temperature (20 °C) achieving nearly 100% selectivity to creosol. These results represent a step forward in advancing the development of more efficient and sustainable processes for bio‐oil upgrading.

Single-atom catalysts are acknowledged for their superior efficiency compared to nanoparticles or clusters, primarily because of the enhanced accessibility of the catalytic center. Essential parameters for assessing their performance are the metal loading degree and the oxidation state of the individual catalytic sites. This is particularly the case in Fe-based Fenton like reaction, in which both Fe2+ and Fe3+ are active but react with significantly different catalytic rates. While the elemental metal loading is easily assessed by elemental analysis, the determination of the oxidation degree is more challenging. To do so, we designed single Fe-based meso-macroporous silica materials as catalysts for the degradation of methylene blue, an organic dye serving as well-known model for the degradation of organic pollutants in wastewater. The silica materials were successfully synthesized by a sol-gel process through a combined templating mechanism with micelles and solid lipid nanoparticles of Fe-based surfactants. Magnetic measurements have revealed that half of the iron centers are in the Fe2+ state. The following of the Fenton like reaction through magnetic measurements agrees with a contribution of Fe2+ in the catalytic process. The magnetic response emerges as a valuable tool for quantifying and characterizing individual catalytic centers.

T cell transmembrane, Immunoglobulin, and Mucin (TIM) are important immune system proteins which are especially present in T-cells and regulated the immune system by sensing cell engulfment and apoptotic processes. Their role is exerted by the capacity to detect the presence of phosphatidyl-serine lipid polar head in the outer leaflet of cellular membranes (correlated with apoptosis). In this contribution by using equilibrium and enhanced sampling molecular dynamics simulation we unravel the molecular bases and the thermodynamics of TIM, and in particular TIM-3, interaction with phosphatidyl serine in a lipid bilayer. Since TIM-3 deregulation is an important factor of pro-oncogenic tumor micro-environment understanding its functioning at a molecular level may pave the way to the development of original immunotherapeutic approaches.

Controlling the activation of the innate immune response, particularly through the use of suitable visible light sources, could pave the way for the development of innovative phototimmunotherapeutic strategies. In this contribution, we investigate the effects of the E/Z isomerization on a phosphatidylserine lipid containing an isomerizable azobenzene moiety, which has recently been shown to regulate the activation of natural killer cells and the production of cytokines [J. Am. Chem. Soc. 2022, 144, 3863−3874]. Specifically, we examine how this isomerization affects interactions with the innate immune system's TIM-3 receptors. Using long-range molecular dynamics simulations with enhanced sampling, we demonstrate that the Z isomer leads to a shallower binding and a less pronounced rigidification of the protein compared to the E isomer and the native lipid, which explains the less pronounced activation of the immune response. ### Competing Interest Statement The authors have declared no competing interest.

Organic dyes-based photothermal agents (OPTAs) has received increasing attention as alternative to inorganic materials due to their higher biocompatibility and extensive diversification. Maximizing non-radiative deexcitation channels is crucial to improve the photothermal conversion efficiency (PCE) of OPTAs. This is typically achieved through individual molecular design or collective enhancement using supramolecular strategies. Furthermore, photothermal therapy (PTT) generally relies on linear one-photon absorption of the light source by the OPTA, with less consideration given to non-linear two-photon absorption (2PA) strategies, despite their potential benefits. Here, a synergistic strategy, which combines intramolecular and intermolecular quenching, is employed to maximize the photothermal efficiency of diphenylamino substituted distyryl dicyanobenzene (DSB), an outstanding two-photon absorbing chromophore. One to three DSB units have been introduced on the conic p-tert-butyl-calix[4]arene (CX), serving as a preorganizing platform to allow aggregates formation and promote intramolecular quenching within the multichromophoric systems. Importantly, the multichromophoric molecules had very high two photon absorption capabilities with cross sections (2PA) reaching maximal values of 3290 GM at 810 nm. Experimental data accompanied by large scale Molecular Dynamics (MD) simulations and Time-Dependent Density Functional Theory (TD-DFT) calculations shed light onto the interaction mechanism in those multiple DSB-appended CX compound to rationalize their optical properties. Then, the formulation with Pluronic F127 amphiphile yields water-dispersible nanoprecipitates (Nps) in which the PCE is further maximized and the photobleaching reduced due to the combination of intra and intermolecular quenching. The high two-photon absorption in the near-infrared (NIR) window associated to high PCE of these nanosized OPTAs could serve as basis to future in vivo 2P-PTT applications.

Eco-friendly approaches for silica production are highly researched to respond increasing industrial demand for bio-nanofillers. Herein, nanosilica of 10-20 nm with mesoporosity was obtained through a mild oxalic acid pre-treatment of millet husk, followed by calcination at 700 degrees C for 2 h. Compared with commercial precipitated silica (CS) and millet husk ash (MHA) directly obtained by calcination of the husk, the pre-treated silica (MHS) had higher purity, revealed using EDX spectroscopy. Moreover, FTIR and Si-29 NMR showed a higher condensation degree in MHS with 73% of Q4 siloxane bonds vs 4% in MHA. The release of the metal and organic impurities from the husk also allows to reduce the crystallinity of MHS, and to increase the specific surface area from 82 m(2)/g in MHA to 238 m(2)/g in MHS. The type II N-2 adsorption-desorption isotherms of MHA and MHS indicate aggregates of non-porous silica particles. MHS also demonstrated remarkable thermal resilience. According to the LCA analysis, MHS has a 40% lower impact on global warming, a 38% lower impact on human carcinogenic toxicity, and a 38% lower impact on terrestrial acidification compared to rice husk nanosilica. This research thus addresses sustainability challenges by repurposing millet husks, which are readily available due to continuous millet cultivation, particularly in India. By reducing the ecological impact of husk disposal through burning, this study offers an economically viable technology for high-purity silica production, aligning with global efforts to combat climate change and promote sustainable practices.

Photothermal therapy (PTT) is a method of growing attention, owing to its controllable process, high efficiency and minimal side effect. Indocyanine Green (ICG) is as Food and Drug Administration (FDA) approved agent that stands on the frontline of further developments of PTT toward clinics. However, the applicability of ICG-mediated PTT is limited by the rapid in vivo clearance and photo-degradation of ICG. To improve those parameters, nanosized ICG-loaded nanoparticles (ICG-J/CX) were fabricated in this study by co-assembly of anionic ICG J-aggregates (ICG-J) with cationic tetraguanidinium calix[4]arene (CX). This very simple approach produces ICG-J/CX with a well-defined nanometer range size and a close to neutral charge. The nanoparticles demonstrate high photothermal conversion efficiency (PCE) and dramatically improved photostability, as compared with ICG. The in vitro cellular uptake and cytotoxicity studies further demonstrated that the ICG-J/CX nanoparticles enhance uptake and photothermal efficiency in comparison with ICG or non-formulated ICG-J, overall demonstrating that ICG-J/CX mediated photothermal therapy have significant potential for attaining cancer treatment.

Surfactants containing fluorocarbon chains have been increasingly studied because they self-assemble into a variety of microscopic and mesoscopic domains and tend to form highly ordered patterns at the air/water interface; these patterns are clearly different from those formed by their hydrocarbon analogs. Focusing on the fluorinated surfactants possessing unique physical characteristics, this review describes the relationship between the line tension and dipole interaction, which is the comprehensive principle governing the pattern formation of two-dimensional self-assemblies. This review further discusses several key experimental and analytical techniques that are useful for characterizing the shape, size, correlation, and viscoelasticity of hierarchical self-assemblies on water surfaces. Finally, several biomedical applications, including biomimetic surface coating, multimodal contrast agents in medical diagnostics, and controlled delivery of gases (O-2 and NO) for oxygenation and antimicrobial effects, are introduced to highlight how the unique physicochemical properties of fluorinated self-assemblies can be applied in materials science.

We report the synthesis and photophysical characterization of biomimetic D-A-D’ cyclocurcumin derivatives, which can potentially be used in light activated chemotherapy. Particularly we highlight that both the donor (D) and acceptor (A) groups significantly influence the photophysical response of the chromophore inducing strong bathochromic shift with D/A strength increase and notable fluorescence quantum yield enhancement with donor strength increase. More important, the nature of the acceptor group (oxo or malonitrile) dramatically modifies the outcome in non-radiative deactivation channels. Indeed, while compounds functionalized with an oxo-moiety undergo ethylenic E→Z photoisomerization, the one bearing a malonitrile group leads exclusively to other non-adiabatic internal conversion channels which much favor photothermal conversion as no isomerization of the ethylenic double bond being observed. The tuning of the photophysical properties and the alteration of isomerization vs. photothermal conversion is rationalized through the analysis of the potential energy surfaces along the most relevant degrees of freedom and shows a competitive pathway over malonitrile rotation. Our results offer novel perspective in oxygen-independent light activated chemotherapy and in the control of photochemical processes in biomimetic chromophores.

The use of photosensitive molecules capable of isomerizing under light stimuli, and thus induce perturbation in biological systems, is becoming increasingly popular for potential light-activated chemotherapeutic purposes. We recently show that a cyclocurcumin derivative (CCBu), may be suitable for light-activated chemotherapy and may constitute a valuable alternative to traditional photodynamic therapy, due to its oxygen-independent mechanism of action, which allows the treatment of hypoxic solid tumors. In particular, we have shown that the E/Z photoisomerization of CCBu correlates with strong perturbations of model lipid bilayers. In this work, we perform all-atom classical molecular dynamics for a more complex bilayer, whose composition is, thus, much closer to eukaryotic outer cell membranes. We have evidenced important differences in the interaction pathway between CCBu and the complex lipid bilayer as compared to previous models, concerning both the membrane penetration capacity and the isomerization-induced perturbations. While we confirm that structural perturbations of the lipid membrane are induced by isomerization, we also show how the use of a simplified membrane model can result in an oversimplification of the system and hinder key physical and biological phenomena. Although, CCBu may be considered as a suitable candidate for light-activated chemotherapy, we also underline how the inclusion of bulkier substituents, inducing larger perturbations upon photoisomerization, may enhance its efficiency.