Search Results (1,342)

Background/Objectives: Hyperthermia coupled with temperature-triggered drug delivery systems, including drug-loaded thermosensitive liposomes, that exhibit increased membrane permeability at hyperthermia-relevant temperatures is a promising therapeutic strategy for cancer treatment. Our previous study revealed that nitrogen-doped carbon dots (CD) partially interact with the phospholipids of liposomes, increasing the membrane permeability of an encapsulated anticancer drug. In vitro cell experiments indicated that their presence in the culture medium, albeit at relatively high concentrations, also affect cell membrane permeability, enhancing drug internalization in cancer cells. This study aims to introduce either hydrophilic or lipophilic carbon dots into liposomes and evaluate them as thermosensitive drug delivery systems. Methods: Alkylated carbon dots (CD-C16) were synthesized and liposomal systems with either the lipophilic CD-C16 or the parent hydrophilic CD were prepared and efficiently loaded with doxorubicin (DOX). Following physicochemical characterization, their thermosensitivity was studied vs. time and temperature, while their effect on cell survival at 37 and 40 °C was evaluated against HEK293 and PC3 cells. Results: At 40 °C, for CD containing liposomes 50% DOX release is observed, whereas for CD-C16 containing liposomes 95% DOX is released within 5 min. Against PC3 cells at 40 °C, both DOX-loaded CD containing liposomes and CD-C16 containing liposomes are more potent compared to the parent drug-loaded liposomes, whereas CD-C16 containing liposomes are equally potent to free DOX. Against HEK293 cells the thermosensitive formulations at 40 °C prove even more cytotoxic, with CD-C16 containing liposomes being more potent than free DOX, but CD containing liposomes are advantageous for being less toxic than free DOX at 37 °C. Conclusions: Although work is needed to elucidate the mechanism at the molecular level, the results suggest that it is possible to adjust liposomal membrane permeability through the incorporation of carbon dots in order to optimize performance for hyperthermia-based applications. Full article

Cannabinol (CBN) is a highly lipophilic phytocannabinoid whose biomedical application is limited by poor water solubility. In this study, colloidal hydroxyapatite nanoparticles (nHAp) were evaluated as a carrier for CBN, and their effect on model lipid membranes was investigated. Interactions between CBN and lipids were examined using Langmuir monolayers and lipid bilayers (black lipid membranes, BLMs). Langmuir monolayer studies revealed strong interactions between CBN and lipids, resulting in changes in isotherms, compressibility, and monolayer stability. BLM measurements indicated that delivery of CBN via nHAp modifies the electrical properties and stability of the lipid bilayer, suggesting alterations in membrane organization and permeability. These results demonstrate that hydroxyapatite nanoparticles can effectively serve as a carrier for cannabinol while modulating its interactions with lipid membranes. Full article

The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating prebiotic conditions. Furthermore, the absence of clear pathways linking primitive amphiphiles to later phospholipid systems highlights the need for chemically continuous intermediate frameworks. Here, we explore borate-bridged amphiphile–carbohydrate conjugates as plausible intermediates between simple prebiotic surfactants and modern lipid bilayers. These conjugates arise from low-molecular-weight polyols—including glycerol, butane-1,2,3,4-tetraol, pentane-1,2,3,4,5-pentaol, and hexane-1,2,3,4,5,6-hexitol—reacting with long-chain alkyl ethers and borate species under alkaline conditions, enabling reversible coupling to ribose and other vicinal diol-containing sugars. This chemistry integrates three essential properties for early compartmentalization: hydrolytically robust ether-linked hydrophobic domains, multivalent and highly hydrated headgroups, and environmentally responsive borate coordination. Comparative physicochemical analysis suggests that single-tail alkylglycerol derivatives preferentially form micelles and interfacial films, while di- and tri-tail tetritol and pentitol conjugates favor lamellar assemblies and vesicle formation across realistic prebiotic pH and salinity ranges. Hexitol-based systems, particularly those bearing three hydrophobic chains, may act as membrane-stabilizing components that enhance rigidity and reduce permeability under extreme conditions. We propose that heterogeneous mixtures dominated by two-tail polyol diethers, supplemented by tri-tail stabilizers and surface-active alkylglycerols, could provide mechanically robust, pH-tunable, and sugar-decorated abiotic membranes. Such borate-mediated amphiphiles offer a chemically coherent framework linking carbohydrate stabilization, ether lipid persistence, and dynamic self-assembly, potentially representing a transitional stage in the evolutionary pathway from primitive amphiphilic films to biologically encoded membranes. Full article

Background: The reliable co-loading of paclitaxel (PTX) and indocyanine green (ICG) into a single lipid nanoparticle (LNP) enables synergistic antitumor delivery but remains challenging due to their distinct physicochemical properties. Methods: This study integrated COSMO-RS calculations, molecular dynamics simulations, and in vitro assays to systematically investigate the effects of lipid composition, drug modification, particle size, and solvent environment on dual-drug loading. Results: This work indicate that DMPS lipid membranes featuring highly polar headgroups and ordered bilayer structures stably bind both ICG and PTX, achieving drug-loading efficiencies (DLEs) of 7.2% and 5.6%, respectively. Carboxylation of PTX enhanced hydrogen bonding with DMPS, while alkyl chain modifications improved membrane insertion, though excessive chain length (e.g., C12) reduced stability due to increased flexibility. Increasing the LNP size from 50 nm to 250 nm raised the DLE of PTX from 4.7% to 8.1%, while sizes beyond 500 nm led to membrane destabilization. The use of 20 vol% ethanol increased total drug loading by 51% by disrupting the hydration shell of ICG and suppressing PTX aggregation; however, ethanol concentrations exceeding 40 vol% intensified drug–solvent competition and weakened membrane binding. Conclusions: This study provides a comprehensive elucidation of the multifactorial regulatory mechanisms underlying dual-drug loading in LNPs, offering a theoretical basis for the rational design of efficient co-delivery systems. Full article

Plant-derived extracellular vesicles (PDEVs) are nanoscale carriers produced through conserved plant mechanisms, including multivesicular body (MVB) formation and consequent extracellular vesicle release. MVBs are formed through repeated rounds of intracellular vesicles’ fusion, thus leading to the incorporation into PDEVs of lipids, proteins, miRNAs, nucleic acids, and secondary metabolites, derived from different cellular compartments. PDEVs possess a bilayer lipid membrane, which protects their cargo from degradation and facilitates membrane–membrane fusion with target cells. Ayurvedic medicinal plants are renowned for their extensive phytochemical diversity and enduring efficacy in addressing inflammation, infections, metabolic disorders, cancer, and neurodegeneration. However, the clinical translation of traditional herbal preparation is severely bottlenecked by batch-to-batch variability, restricted compound bioavailability, mechanistic uncertainties, and limitations of conventional large-scale extractions. This perspective research study critically proposes PDEVs as an innovative interpretation for Ayurvedic medicinal plants utilization. We identify and evaluate medicinal plants with established therapeutic characteristics that remain unexamined in PDEV research, hence presenting compelling opportunities for future investigation. By establishing a synergistic bridge between ancient Ayurvedic knowledge and modern nanomedicine, this perspective provides a methodological roadmap to guide health-efficient plant selection and accelerate translational research in next-generation therapeutics. Full article

Bacterial β-barrel pore-forming toxins, including Staphylococcus aureus α-toxin (Hla) and Bacillus cereus toxins hemolysin II (HlyII) and cytolytic toxin K2 (CytK-2), are secreted by bacterial cells as water-soluble monomers. These monomers assemble within lipid bilayers to form cylindrical pores, leading to lysis of target eukaryotic cells. We created mutant forms of these toxins that, based on the results of X-ray structural analysis of Hla and the prediction of the 3D structure of HlyII and CytK2, can form intramolecular disulfide bonds in monomers. The substitutions were made in the region responsible for toxin insertion into the target membrane. The mutant forms reversibly altered their hemolytic activity depending on the presence of reducing reagents and were non-toxic when injected into experimental animals. The immune response to injection of the mutant forms of Hla and CytK-2 toxins resulted in higher antibody titers against the wild-type toxins and a higher level of immunological memory than with injection of the HlyII mutant. The mutant form of CytK-2 demonstrates the properties of a prototype vaccine, as immunization with this protein protects animals against the effects of the wild-type toxin. Full article

The molecular chaperone paradigm has shaped modern views of assisted protein folding, yet it does not fully capture the physical context in which de novo folding occurs in cells. A defining feature of the cellular milieu is macromolecular tethering in cis, whereby nascent polypeptides remain physically linked—through covalent or persistent associations—to ribosomes, lipid bilayers, or pre-folded domains of multidomain proteins. Because molecular chaperones have traditionally been defined as reversible binders acting in trans, this cis-acting mode has remained conceptually underappreciated. Cellular macromolecules, by virtue of their steric bulk and surface charges, can suppress aggregation of tethered polypeptides, thereby increasing productive folding yield. By analogy to colloidal stability, this repulsion-mediated control of aggregation suggests that cellular macromolecules can exhibit intrinsic chaperone-like activity largely independent of whether the linkage occurs in cis or in trans. This property provides a conceptual basis for linking cis- and trans-acting chaperoning. Thus, macromolecular tethering in cis may constitute a built-in layer of cellular chaperoning, distinct in physical linkage yet mechanistically related to conventional molecular chaperones. Full article

Graphene oxide (GO)–lipid hybrid nanostructures represent a promising class of multifunctional platforms for drug delivery and fluorescence-guided cellular imaging. In this study, we developed a graphene oxide-supported lipid bilayer system composed of rhodamine-labeled phosphatidylcholine (POPC-Rhod) for the delivery of the repurposed antispasmodic drug alverine citrate (ALV) to neuroblastoma cells. The hybrid nanostructures were assembled using two drug-loading strategies and characterized by UV–Vis spectroscopy, fluorescence analysis, dynamic light scattering, and atomic force microscopy to evaluate molecular interactions, vesicle size distribution, and nanomechanical properties. In vitro studies were performed using human neuroblastoma SH-SY5Y cells and their retinoic acid-differentiated neuronal-like counterparts. Confocal microscopy confirmed efficient cellular uptake of the fluorescent lipid–graphene hybrids, while viability and mitochondrial reactive oxygen species assays revealed differentiation-dependent cellular responses. ALV-loaded hybrids induced cytotoxic effects in proliferating neuroblastoma cells, whereas differentiated neuron-like cells exhibited greater tolerance and, at moderate concentrations, preserved viability despite increased oxidative stress. These findings demonstrate that graphene oxide–lipid hybrids can act as fluorescence-traceable drug delivery platforms and highlight the potential of alverine as a candidate for repurposing in neural cancer models. The system presented here provides a proof-of-concept framework for the development of multifunctional nanocarriers integrating therapeutic delivery with imaging capabilities. Full article

Extracellular vesicles (EVs) derived from microbial sources, including beer yeast (Saccharomyces cerevisiae), have recently attracted increasing attention as bioactive nanostructures with potential biomedical and cosmetic applications. In this study, EVs were isolated from Saccharomyces cerevisiae (beer yeast) using an electrokinetic ion-binding filtration system, followed by tangential flow filtration (TFF)-based buffer exchange. Their physicochemical characteristics and hair follicle-related biological activities were systematically evaluated. Nanoparticle tracking analysis demonstrated a mean particle size within the typical EV range, and zeta potential analysis confirmed a negatively charged surface. Cryo-transmission electron microscopy further verified the presence of lipid bilayer-enclosed nanovesicles. Biological activity was assessed in human dermal papilla cells, keratinocytes, and dermal fibroblasts, which collectively represent key components of the hair follicle microenvironment. At non-cytotoxic concentrations, yeast-derived EVs enhanced dermal papilla cell proliferation and promoted keratinocyte migration. The EVs attenuated pro-inflammatory cytokine expression under stimulated conditions and upregulated collagen-related gene expression in dermal fibroblasts. In addition, measurable antioxidant activity was observed. Collectively, these findings indicate that S. cerevisiae-derived extracellular vesicles exhibit multifunctional bioactivity relevant to the regulation of hair follicle-associated cellular processes. This study supports the potential of microbial EVs as scalable bioactive platforms for modulating hair follicle microenvironmental homeostasis. Full article

Cyclotides are exceptionally stable plant peptides whose biological activity is widely attributed to interactions with lipid membranes, yet the molecular mechanisms underlying these interactions remain incompletely resolved. Here, we employ microsecond-scale (1 μs) all-atom molecular dynamics simulations to investigate the membrane association of the cyclotide kalata B1 with phospholipid bilayers of distinct headgroup composition, including POPC, POPE, and POPG. This extended timescale enables full bilayer equilibration and allows observation of slower peptide-induced membrane responses that are not accessible in shorter simulations. Across all systems, kalata B1 rapidly adsorbs to the membrane surface and remains predominantly surface-associated throughout the simulations, while the cyclic cystine knot motif remains structurally intact, confirming the exceptional robustness of the cyclotide fold during membrane engagement. Lipid-dependent differences arise primarily from variations in peptide orientation, conformational flexibility, and interfacial dynamics rather than deep bilayer insertion or pore formation. Zwitterionic POPC membranes favor compact, upright peptide configurations, whereas POPE and POPG bilayers promote enhanced lateral spreading and dynamic reorganization driven by hydrogen bonding and electrostatic interactions, respectively. Leaflet-resolved analyses of lipid contacts, membrane thickness, and area per lipid reveal localized, asymmetric perturbations confined to the peptide-exposed leaflet, with no evidence of sustained bilayer thinning or global destabilization. Together, these results support an interfacial, headgroup-dependent mechanism of cyclotide membrane activity and reconcile previous experimental observations. This work provides molecular-level insight into lipid selectivity and early-stage cyclotide–membrane interactions that may inform future design of cyclotide-based bioactive agents. Full article

Kaurenoic acid (KA) is an ent-kaurane diterpenoid present in several medicinal plant species and has been reported to exhibit anti-inflammatory, cytotoxic, and analgesic activity in experimental models. Despite its pharmacological profile, the development of KA as a therapeutic agent has been hindered by its unfavorable physicochemical and biopharmaceutical properties. KA is highly lipophilic and poorly soluble in water, which limits its dissolution, systemic exposure, and oral bioavailability. These limitations are common among plant-derived bioactive compounds and pose significant challenges for clinical development. Lipid-based nanocarrier systems, particularly liposomal formulations, have therefore been investigated as potential delivery strategies for improving the biopharmaceutical performance of KA. Encapsulating KA within phospholipid bilayers can improve its apparent solubility, protect it from degradation, and modify its biodistribution compared to the free compound. In this review, we discuss the pharmacological mechanisms of KA, its physicochemical properties, and the biopharmaceutical barriers to its therapeutic development. We also critically evaluate published studies on nanocarrier-based formulations, focusing on encapsulation efficiency, particle size, release properties, and pharmacokinetics (PK). Additionally, regulatory and pharmaceutical considerations relevant to lipid-based delivery of KA are addressed. Available evidence supports lipid-based nanocarriers as a promising strategy to improve preclinical development and formulation performance of poorly soluble plant bioactives such as kaurenoic acid. Although KA-loaded nanocarriers demonstrate encouraging activity in preclinical models, comprehensive pharmacokinetic and safety evaluations remain necessary before clinical development can be realistically considered. Full article

Curcumin, a natural polyphenol derived from Curcuma longa, is widely recognized for its therapeutic properties. However, its clinical utility is limited because of poor solubility, rapid degradation and hence low bioavailability. To overcome these issues, nanoformulation approaches, especially PEGylated liposomes, have been explored as advanced delivery systems. PEGylation, which involves attaching polyethylene glycol (PEG) to the liposomal surface, enhances circulation time by creating a steric shield that reduces protein interactions and clearance by the mononuclear phagocyte system (MPS). However, PEG can alter lipid membrane properties, which may in turn affect curcumin’s solubility and distribution within the liposomal bilayer, ultimately reducing its loading efficiency. To ensure that PEG-modified liposomes can be effectively loaded with curcumin, we investigated curcumin–membrane interactions in saturated (DMPC) and unsaturated (POPC) liposomes, both in the presence and absence of PEG. Based on dissociation constants (K_d) obtained from fluorescence spectroscopy measurements, we found that PEGylated DMPC liposomes exhibit the strongest binding affinity for curcumin. Fluorescence quenching experiments showed that curcumin adopts a transbilayer orientation in all membranes examined. Curcumin’s location within PEGylated and non-PEGylated liposomal membranes was further confirmed by examining its effects on membrane properties, including fluidity, polarity, and oxygen transport. These effects were investigated using electron paramagnetic resonance (EPR) spectroscopy with spin labels. The results indicate that PEG does not impose major changes on membrane properties. Curcumin, however, was found to reinforce the liposomal membranes, increase their polarity, and reduce oxygen availability. Overall, the findings suggest that liposomes, particularly those composed of PEGylated DMPC, are effective vehicles for curcumin delivery. Full article

This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, and multifunctional hybrids. Model membranes span Langmuir monolayers, supported lipid bilayers, vesicles/liposomes across sizes, and emerging hybrid or asymmetric constructs that better approximate native complexity. Mechanistically, interactions follow recurrent routes—surface adsorption, bilayer insertion, pore formation, and lipid extraction/reorganization—regulated by particle size, morphology, charge, ligand architecture, and lipophilicity, in conjunction with membrane composition, phase state, curvature, and asymmetry. A multiscale toolkit links structure, mechanics, and dynamics: Langmuir troughs and Brewster Angle Microscopy map thermodynamics and mesoscale morphology; atomic force microscopy and quartz crystal microbalance with dissipation resolve nanoscale topography and viscoelasticity; fluorescence microscopy/spectroscopy reports on localization and packing; neutron and X-ray reflectometry quantify vertical structure; molecular dynamics provides atomistic pathways and design hypotheses. Historically, the field advanced from early monolayers and bilayers, through the fluid mosaic model, to raft microdomains and modern biomimetic systems, enabling increasingly realistic experiments. Key advances include cross-method integration linking experimental observations with image-based computational models; persistent debates concern the translation from simplified models to living membranes, the role of dynamic coronas, and scale/force-field limits in simulations. Future efforts should prioritize hybrid models incorporating proteins and asymmetric lipidomes, standardized reporting and reference systems, rigorous coupling of experiments with calibrated simulations and machine learning, and alignment with safety-by-design and regulatory expectations, thereby shifting interfacial measurements from descriptive observation to predictive design rules. Full article

Liposomes, spherical bilayer lipid-containing vesicles, are promising nanocarriers used for constructing drug delivery systems (DDS). Various strategies can be employed to loosen or break the liposome and release drugs as the tumor cells-targeting DDS made of liposomes reach the targeted sites. One of the most commonly used strategies is to heat the liposomal DDS by letting the gold nanoparticles or other light-absorbing substances that partition in various portions (inner water core, lipid bilayer or outside) of the liposome absorb light irradiation. Then, which portion can lead to the largest liposome structure change due to the same temperature variation? The answer is essential to aid the design of liposomal DDS; thus, wet lab experiments were carried out. However, even though irradiation-absorbing substances in different portions were irradiated for the same time and with the same irradiation intensity, it was impossible to ensure the three portions have the same temperature increase in the experiments. Furthermore, it is impossible to learn the related micromechanism and molecular-level details of the effects of temperature changes on the liposome structure with experimental methods. The molecular dynamics (MD) method is extensively employed by researchers to obtain in-depth molecular-level insights. Most researchers tend to simulate only a planar lipid bilayer structure, but Amărandi et al. demonstrated that such simplification strategy may give wrong simulation results contrary to the experimental results. Though Jämbeck et al. and Zhu et al. established whole spherical liposome systems with a diameter of about a dozen nanometers and simulated the systems with MD simulations, they did not simulate temperature-relevant properties of the liposome. Therefore, currently there is a lack of research on simulating the structure change in a whole spherical liposome due to temperature variations. So, we established the whole spherical structure of the liposome, simulated how it changes with temperatures and obtained molecular-level research results. It is observed that the temperature increase in the lipid bilayer causes the largest increase in lipid strand sway amplitude, the largest changes in lipid positions, the largest decrease in the distribution density of lipids and water around a lipid and the largest decrease in the interactions between lipids and lipids and between lipids and water, leading to the largest change in the liposome structure. We also studied how the degree of lipid tail unsaturation affects liposome structure changes with temperatures. Due to the C3 kinks in the unsaturated lipid tails, the distribution density of unsaturated lipids is not as high as saturate ones, leading to smaller attraction interactions and consequently larger liposome structure change with temperature. The obtained results are useful for the liposomal DDS design for the purpose of improving DDS performances and delivery outcomes. Full article

Monoenoic fatty acids (MUFAs), defined by the presence of a single carbon–carbon double bond within a long aliphatic chain, constitute a structurally diverse and ecologically significant class of lipids widely distributed in aquatic organisms. In marine and freshwater environments, MUFAs are fundamental components of membrane phospholipids and storage lipids, where mono-unsaturation modulates melting point, lipid packing, and bilayer dynamics, enabling homeoviscous adaptation to fluctuations in temperature, pressure, salinity, and oxygen availability. Positional and geometric isomerism (e.g., cis-Δ5, Δ7, Δ9, Δ11, Δ13, and trans forms) further enhances biochemical diversity, providing sensitive chemotaxonomic markers and indicators of trophic transfer across food webs. In addition to common straight-chain monoenes, rare methyl-branched, cyclopropane-containing, and acetylenic derivatives occur in specialized aquatic taxa, reflecting evolutionary adaptation and ecological niche differentiation. Computational QSAR analyses suggest that monoenoic fatty acids and their unusual analogues occupy bioactivity spaces associated with lipid metabolism regulation, vascular and inflammatory modulation, antimicrobial defense, and membrane stabilization. This review integrates structural chemistry, biosynthesis, ecological distribution, trophic dynamics, and predicted biological activity of monoenoic fatty acids in aquatic systems, highlighting their dual role as adaptive membrane constituents and as biologically active mediators linking molecular lipid architecture to hydrobiological function and environmental change. Full article