The catalytic activation of CO2 under mild conditions to form value-added heterocyclic products is of paramount interest. Copper sulfides are a large class of materials, many of which are found as minerals in nature. They often show remarkable physical properties, and further studies of their catalytic properties need to be conducted. The simple compound Cu2S was designed, its synthesis was improved, and its catalytic activities in CO2 activation are disclosed here. Synthesized Cu2S is shown to be an efficient heterogeneous catalyst for the carboxylation of propargylamines under ambient temperature and pressure conditions and the carboxylation of terminal alkynes under one atm CO2 at 80 degrees C. CO2 is transformed into high-value-added chemicals with a wide range of substrates with excellent yields, and the catalyst is easily reused at least 5 times without significant activity reduction. The catalytic and recycling performances are significantly better for synthesized Cu2S compared to those of its commercial analogue. In summary, Cu2S is a new catalyst that is simple, non-toxic, self-supported, recyclable, and practical. These findings open a general route to the catalytic properties of Cu2S toward, not only mild CO2 activation applications, but also a variety of other useful reactions.

Mesoscale interactions critically shape the biological identity of extracellular nanoparticles, including extracellular vesicles. These interactions encompass biomolecular coronas, transient aggregation, and fusion events. Among them, the interaction between extracellular vesicles and lipoproteins has recently garnered significant attention due to their potential impact on functionality and in vivo fate of extracellular vesicles. In this work, we present a first investigation of the binding between human red blood cell-derived extracellular vesicles and lipoproteins across multiple scales, in both buffer and plasma. Red blood cell-derived extracellular vesicles were selected as a model system for their physicochemical homogeneity, potential in personalized medicine, and production scalability. To achieve this, we employed an ad hoc suite of orthogonal analytical techniques: fluorescence cross-correlation spectroscopy (FCCS), super-resolution microscopy, flow cytometry, and Single Molecule Array assays (Simoa). Our results reveal class-specific and context-dependent extracellular vesicle-lipoprotein associations. Notably, lipoproteins bind to extracellular vesicles with affinities ranging from 10 nM to 1 μM and with up to 100% extracellular vesicles interacting with high-density lipoproteins in the presence of plasma proteins. These findings uncover a complex and dynamic interactome of red blood cell-derived extracellular vesicles across lipoprotein classes. This work establishes a robust methodological framework for studying mesoscale interactions of extracellular nanoparticles under physiologically relevant conditions. Its versatility allows for its application to diverse interaction scenarios, supporting systematic investigation of context-dependent effects on EV-LP binding.

The polyallylamine hydrochloride (PAH) polymer is here functionalized with branched and biocompatible polysaccharide dextran (DEX) molecules. Covalent conjugation of DEX to PAH has been achieved through a straightforward reductive amination approach, allowing for a controlled number of DEX chains per PAH polymer (PAH:DEXn, n = 0.1, 0.5, 1, 2, 5, 10). When exposed to phosphate buffer, PAH:DEXnpolymers form supramolecular assemblies. Physico chemical characteristics and pH responsiveness of the assemblies are correlated with the number of dextran chains per PAH molecule. Nanocapsules (NCs) are formed when PAH:DEX ratio is 1. Capsule formation is explained by the branched nature of DEX and steric consideration ruling the organization of polyamine chains in phosphate buffer. NCs and glyconanoparticles formed with n < 1 are responsive to pH changes, being disassembled at endosomal pH < 6 and reassembled when 6 < pH < 9. Dynamic light Scattering (DLS), zeta-potential measurements, cryo-Electron Microscopy and Small Angle X-ray Scattering (SAXS) provided key information about their structure, morphology, size, polydispersity, surface charge, and stability over time. Protein entrapment into the NCs and pH-dependent release is demonstrated with bovine serum albumin (BSA) as model protein by diffusion measurements in fluorescence correlation spectroscopy (FCS), following changes in BSA conformation before and after triggering NC disassembly by circular dichroism (CD), and comparing NCs SAXS fingerprints with and without BSA. Our results show novel assemblies based on polyamine phosphate interactions with capacity of loading large molecules through the formation of capsules, which may find applications in the endosomal delivery of therapeutic proteins and enzymes.

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH2 (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer. DX is trapped in the peptide regions of the assemblies. Confocal laser scanning microscopy shows that the peptide assemblies translocate into the nucleus. Cytotoxicity studies over 72 h in A549 and HeLa cancer cell lines show less toxicity for the LP encapsulated DX than for free DX. In contrast, subtoxic doses of encapsulated DX are more effective than free DX in avoiding colony formation over 14 days, with a complete absence of colonies for the LP-encapsulated DX. The results show a more efficient and slow delivery of DX to the nucleus through LP encapsulation, paving the way for the use of lower DX doses as a chemotherapeutic agent.

Initially observed on synthetic nanoparticles, biomolecular corona existence and role in determining nanoparticle identity and function are now beginning to be acknowledged in biogenic nanoparticles, particularly in extracellular vesicles. We have developed here a methodology based on Fluorescence Correlation Spectroscopy to track biomolecular corona formation on extracellular vesicles derived from red blood cells and placental mesenchymal stromal cells when these vesicles are dispersed in human plasma. The methodology allows for the study of corona dynamics in situ in physiological conditions. Results evidence that the two extracellular vesicle populations feature distinct corona dynamics, with red blood cell-derived extracellular vesicles exchanging a higher number of proteins. These findings indicate that the dynamics of the biomolecular corona may ultimately be linked to the cellular origin of the extracellular vesicles, revealing an additional level of heterogeneity, and possibly of bionanoscale identity, that characterizes circulating extracellular vesicles.

BACKGROUND:Propolis is a complex resinous material collected by bees from plant sources and known for its rich content in bioactive phenolic compounds, including flavonoids and aromatic acids. Its chemical composition and biological activity are highly influenced by the botanical and environmental conditions surrounding the beehives. In Colombia, limited studies have addressed the chemical diversity and therapeutic potential of propolis from regions with high altitudinal variation such as Tolima. RESULTS:In this study, three propolis ethanolic extracts (PrEE1, PrEE2, PrEE3) were obtained from hives located at different altitudes in Tolima, Colombia (1250, 1100, and 900 m above sea level (a.s.l.), respectively). Samples were analyzed for total phenolic content (TPC), total flavonoid content (TFC), antioxidant capacity (DPPH, ABTS, FRAP), antimicrobial activity (disk diffusion and minimum inhibitory concentration), and cytotoxicity in A549, WI-38 and NIH-3 T3 cell lines. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis revealed a distinct phytochemical profile for each extract. PrEE1 had the highest TPC (130.2 g GAE kg-1) and TFC (6.70 g QE kg-1), and strong antioxidant activity with DPPH scavenging of 89.2%. It also exhibited potent antimicrobial activity against Staphylococcus aureus and Candida albicans, and selective cytotoxicity toward A549 lung cancer cells. In contrast, PrEE3 had lower phenolic content but contained unique polyprenylated benzophenones. CONCLUSION:The results indicate that altitude significantly influences the chemical and biological properties of Colombian propolis. Propolis from higher altitudes, such as PrEE1, is a promising natural source of multifunctional bioactive compounds with antioxidant, antimicrobial, and anticancer potential for pharmaceutical and nutraceutical applications. © 2025 Society of Chemical Industry.

Multifunctional biomaterials based on natural polymers are promising for biomedical applications. Herein, silk fibroin (SF) and chitosan (Ch) films were prepared by solvent casting and characterized regarding their structural, mechanical, and biofunctional properties. The SF/Ch blend exhibited tuneable features by combining the mechanical strength of SF with the hydrophilicity and bioadhesion of Ch. DMSO acted as a plasticizer, promoting β-sheet formation and flexibility. A key innovation is the selective dendronization of one film surface using a Newkome-type dendron, confirmed by FTIR-ATR and AFM, which enabled asymmetric surface functionalization. As a proof of concept, fluorescein was successfully incorporated into the films, and its homogeneous distribution and retention were evidenced through UV-Vis and confocal microscopy. This result highlights the potential of the developed matrices for drug loading and delivery. Furthermore, the cytocompatibility was confirmed in vitro using fibroblast and keratinocyte cell lines. By merging biocompatibility with functional versatility, this work positions SF/Ch dendronized films at the forefront of innovative strategies for wound healing and drug delivery.

We report a novel deposition pathway for barium titanate (BTO) onto hydrophobically coated cobalt ferrite (CFO) nanoparticles, resulting in the formation of magnetoelectric core-shell nanoparticles. Our strategy utilizes a bimetallic Ba and Ti oleate (BTOle) precursor, which hydrophobically interacts with dimethyldioctadecylammonium bromide (DDAB)- stabilized CFO particles during an interfacial phase transfer step. Thermal post-treatment yields a crystalline structure comprising distinguishable BTO and CFO phases, with BTO adopting a distorted cubic to tetragonal crystal phase. Magnetoelectric characterization yields a millivolt voltage-range output, associated with the mechanical coupling between the piezoelectric and magnetostrictive phases. This method circumvents traditional sol-gel limitations and phase transfer hurdles, offering a streamlined route for fabricating magnetoelectric nanoparticles. Our results suggest magnetoelectric particles are suitable for incorporation in wireless actuation technologies.

Surface coatings with polyethylene glycol (PEG) polymers have often been employed to improve nanoparticles (NPs) biocompatibility and extend circulation time by reducing protein adsorption. PEGylated NPs benefit from steric hindrance and repulsion effects, which are influenced by PEG molecular weight, density, and chain conformation. However, repetitive exposure to PEG can trigger acute and chronic immunological responses as a result of the development of Immunoglobulin G anti-PEG antibodies. NPs functionalisation with glycans has become an emerging approach to increase their biocompatibility as these biomolecules are highly hydrophilic, biocompatible interact with biological receptors expressed in the body, and can be conjugated, controlling their orientation. In this study, we developed a series of gold NPs (AuNPs) coated with PEG linkers of different lengths and conjugated with mannose (Man) or sialic acid (Sia) glycans, and we carried out a detailed characterisation prior to and after exposure to biological fluids to study their behaviour and protein corona formation. Our findings show that the glycan-coated NPs exhibit stabilisation after protein interaction, with Man coatings showing the lowest protein affinity and that the glycans are biologically active and capable of binding to glycan receptors (such as Concanavalin A) despite the presence of a complex protein environment. Results indicate that glycan modification of PEGylated NPs reduces nonspecific interactions while preserving active targeting properties, underscoring their potential for therapeutic applications.

Despite its potential in hydrogen (H2) therapy, ammonia borane (AB) has limited biomedical applications due to its uncontrolled hydrolysis rate and potential to cause cytotoxicity. Existing material-based delivery strategies focus on accelerating AB hydrolysis for H2 production, hence exacerbating these issues. A new nanoconfinement strategy is reported, which loads AB onto oxygen-deficient, hybrid-phased titanate nanocrystals on implant surfaces through a unique one-end-anchored docking (OEAD) mechanism. This nanoconfinement strategy effectively restricts the release of AB molecules, allowing only water molecules to infiltrate the interlayer space for slow hydrolysis and sustained H2 release. This significantly prolongs the duration of H2 release and effectively circumvents the cytotoxicity associated with AB interacting with hydrogen peroxide (H2O2) in the inflammatory microenvironment. In vitro and in vivo have shown that sustained H2 release from the implant surface effectively alleviates diabetes-related oxidative stress, and combined with the release of magnesium ions (Mg2+) synergistically promotes innervated-vascularized bone regeneration.

Unspecific uptake by the liver is one of the main drawbacks of the translation of nanomaterials into clinics, preventing their delivery into diseased tissues. Here, we synthesized gold nanoparticles (GNPs) decorated with a sialic acid-displaying glycopeptide to enhance their specific targeting properties by reducing their uptake inside hepatic cells. We demonstrated the biocompatibility of the glycopeptide-coated GNPs with two different nanomaterial shapes (spherical and rod-like GNPs) and the targeting properties of the glycopeptide were retained in serum-free and protein-rich media. We found that the glycopeptide reduces nanomaterial interaction with hepatic cells by 1.96 times. In the liver, Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) were the only cells that interacted with the GNPs, increasing the expression of sialic acid-binding receptors such as Siglec-1. This work provides potential new strategies to overcome off-target nanomaterial accumulation by manipulating nanomaterial functionalisation with glycans to alter hepatic cell interactions.

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration.

Among therapeutic peptides, antimicrobial peptides (AMPs) have gained significant attention for their potential to combat antimicrobial resistance. Their efficacy often relies on the ability to adopt organized structures, such as alpha-helices or beta-strands. However, the formation of supramolecular aggregates can hinder their antimicrobial effectiveness. This study explores the correlation between supramolecular organization in phosphate buffer (PB) and biological activity in three cationic peptides with identical amino acid compositions, nine Leu-Lys pairs, but differing architectures: linear and branched, using lysine or a triazine as the branching unit. Structural conformation and self-assembly behaviors in water and PB were analyzed using Circular Dichroism (CD), Dynamic Light Scattering, and Atomic Force Microscopy (AFM). Results show that the linear peptide, largely unstructured or randomly coiled in water at neutral pH, adopts a beta-sheet conformation in PB. AFM imaging revealed that at low peptide and phosphate concentrations, the linear peptide showed small helical rods self-assembled via beta-sheet interactions. This structural transition is driven by electrostatic interactions between phosphate ions and the amine group. The linear peptide, which lacks antibacterial activity, shows a strong tendency to form large beta-strand aggregates. In contrast, branched peptides were less prone to aggregation and showed enhanced antibacterial activity, particularly the triazine-branched peptide.

Background: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo. Methods: HNP were prepared by the self-assembly of a methoxy-poly (ethylene glycol)-block-poly (L-glutamic acid) copolymer (PEG-pGlu) and the coprecipitation of CaPO4 to incorporate siRNA. The in vitro cell viability and migration were evaluated prior to in vivo experiments. Further, animals bearing early-stage and advanced Luminal A breast cancer were treated with HNP-siHOXB7, HNP-siHOXB7 + TMX, and TMX. Antitumoral activity and gene expression were evaluated following histopathological, hematological, and biochemical analysis. Results: The HNP were efficient in delivering the siRNA in vitro and in vivo, whilst HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity. Conclusions: Therefore, our findings suggest that HOXB7 can be an interesting molecular target for Luminal A breast cancer, especially associated with hormone therapy, aiming for adverse effect mitigation and higher therapeutic efficacy.

Hypothesis The anticancer drug doxorubicin hydrochloride (DX) shows a high solubility in aqueous media thanks to the positive charge in the ammonium group. This feature, however, affects the drug encapsulation in the hydrophobic domains of polymeric micelles (PMs) used for the targeted delivery of the drug. At basic pH, DX deprotonates but also acquires a negative charge in the phenolic groups of the anthracycline structure. Both the efficiency and the rate of encapsulation will be increased by choosing an appropriate pH such that the drug molecule is in neutral form.Experiments An optimal pH for the encapsulation of the DX in PMs based on commercial poloxamers and on the diblock copolymer methoxy-poly(ethylene glycol)17-b-poly(ε-caprolactone)9 was determined by fluorescence spectroscopy, following the time evolution of both the intensity ratio of the first and the second emission bands of DX and its fluorescence lifetime, both sensitive to the environment polarity. Intracellular delivery of PMs encapsulated drug was followed by Confocal Scanning Laser Microscopy (CSLM). Cell viability was assessed with the sulforhodamine B (SRB) assay.Findings By adjusting pH to 8.1 a high yield of incorporation of DX in the PMs was achieved coupled to an appreciable increase (one order of magnitude) in the drug encapsulation rate. In-vitro tests in selected cancer cell lines showed the slow release of the drug and a delay in the cytotoxic response in comparison to free DX as detected by CSLM and SRB assay. The proposed methodology paves the way for a greener, faster and more efficient encapsulation of DX in PMs.

The Cu-glutathione (GSH) redox system, essential in biology, is designed here as a supramacromolecular assembly in which the tetrahedral 18e Cu(I) center loses a thiol ligand upon adsorption onto ZIF-8, as shown by EXAFS and DFT calculation, to generate a very robust 16e planar trigonal single-atom Cu(I) catalyst. Synergy between Cu(I) and ZIF-8, revealed by catalytic experiments and DFT calculation, affords CO2 conversion into high-value-added chemicals with a wide scope of substrates by reaction with terminal alkynes or propargyl amines in excellent yields under mild conditions and reuse at least 10 times without significant decrease in catalytic efficiency.

The Biomolecular Corona (BC) is a typical phenomenon that occurs at the interface between the nanomaterial and the surrounding media, involving the adsorption or the desorption of macromolecules at this interface. Studying BC dynamic properties on soft nanomaterials (i.e., liposomes or extracellular vesicles) proves to be challenging. Advancing in situ methodologies for investigating BC on soft nanoparticles is essential for elucidating the intricate interplay between surface composition, properties, and dynamic BC formation. In this study, we present new evidence of distinct dynamics in BC formation for two extracellular vesicle (EV) subtypes. Utilizing Fluorescence Correlation Spectroscopy (FCS) coupled with a fluorescent monoclonal antibody as a corona probe enabled the characterization of macromolecule exchange at the EV surface and the dynamic evolution of the BC.

HYPOTHESIS:Lipopeptides synthesized from the Nucleolar Targeting Peptide (NrTP6) with one, two or four dodecanoic fatty acid (FA) chains, display large head to tail volumes, which together with the number of lipid chains per molecule, impacts their self-assembly behavior. In phosphate buffer (PB), peptide to peptide interactions are triggered by the presence of phosphate ions that act as ionic crosslinkers, affecting the organization of the lipid assemblies.EXPERIMENTAL:The NrTP6 lipopeptides were synthesized by the solid phase peptide synthesis technique. The critical micellar concentration (CMC) of the lipopeptides was determined in water and PB by pyrene fluorescence. The size and morphology of lipopeptide assemblies were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Circular dichroism (CD) was used to study the secondary structures of the lipopeptide assemblies.RESULTS:For NrTP6 lipopeptides with two and four lipid chains, CMCs in water are larger than in PB. TEM images of the lipopeptide assemblies show different morphologies including fibers, rods, and spheres depending on the number of lipid chains, concentration and whether they are assembled in water or PB. CD spectroscopy shows that the peptide conformation, either random or beta, correlates with the morphology of the assemblies.

Multiresponsive hydrogels are valuable as biomaterials due to their ability to respond to multiple biologically relevant stimuli, i.e., temperature, pH, or reactive oxygen species (ROS), which can be present simultaneously in the body. In this work, we synthesize triple-responsive hydrogels through UV light photopolymerization of selected monomer compositions that encompass thermoresponsive N-isopropylacrylamide (NIPAM), pH-responsive methacrylic acid (MAA), and a tailor-made ROS-responsive diacrylate thioether monomer (EG3SA). As a result, smart P[NIPAMx-co-MAAy-co-(EG3SA)z] hydrogels capable of being manufactured by digital light processing (DLP) 4D printing are obtained. The thermo-, pH-, and ROS-response of the hydrogels are studied by swelling tests and rheological measurements at different temperatures (25 and 37 °C), pHs (3, 5, 7.4, and 11), and in the absence or presence of ROS (H2O2). The hydrogels are employed as matrixes for the encapsulation of ketoprofen (KET), an anti-inflammatory drug that shows a tunable release, depending on the hydrogel composition and stimuli applied. The cytotoxicity properties of the hydrogels are tested in vitro with mouse embryonic fibroblasts (NIH 3T3) and RAW 264.7 murine macrophage (RAW) cells. Finally, the anti-inflammatory properties are assessed, and the results exhibit a ≈70% nitric oxide reduction up to base values of pro-inflammatory RAW cells, which highlights the anti-inflammatory capacity of P[NIPAM80-co-MAA15-co-(EG3SA)5] hydrogels, per se, without being necessary to encapsulate an anti-inflammatory drug within their network. It opens the route for the fabrication of customizable 4D printable scaffolds for the effective treatment of inflammatory pathologies.

Nanogels (NGs) are synthesized by precipitation polymerization of dendritic polyglycerol (dPG), N-isopropylacrylamide (NIPAM), and N-isopropyl methacrylamide (NIPMAM). The stabilization and agglomeration of subunits during the NG growth result in raspberry-like structures, as shown by transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering measurements. Positive charges are introduced into dPG-NIPAM-NIPMAM NGs by (1) the copolymerization of dimethylaminoethyl methacrylate (DMAEMA) and (2) the copolymerization of glycidyl methacrylate (GMA), followed by its functionalization with ethylenediamine (ED) through the epoxy group. Homogeneous structures are obtained by the copolymerization in batch of DMAEMA with the other monomers, whereas core-shell NGs are reached by semibatch copolymerization of GMA. After amination, the charges are restricted to the core of the NGs.