Early, reliable detection of α-synuclein (αSN) is critical for Parkinson's disease diagnosis, yet antibody-based assays remain limited by sensitivity, matrix effects, and cost. We report a label-free aptamer–gold nanoparticle nanobiosensor (G12Apt@AuNP) for non-invasive αSN detection in saliva. Molecular docking identified F5R1 as the aptamer with the most favorable predicted binding affinity; a dodeca-guanine (G12) was appended to provide colloidal stabilization and to control conjugation and orientation on the AuNP surface. Interaction with αSN monomers, oligomers, and fibrils produced a concentration-dependent plasmonic red-shift arising from αSN-induced nanoparticle aggregation. Conditions were optimized by Taguchi design and ANOVA. Across 8 pM–8 μM, the platform achieved an 8 pM detection limit and a 0.8 nM–0.8 μM linear range for 24 h aggregated αSN, comparing favorably with reported label-free optical aptasensors. It showed high selectivity against related proteins and detectable responses in spiked saliva at 4 nM, supporting development toward clinical synucleinopathy detection.
The melting of finite-sized two-dimensional (2D) clusters is ubiquitous in nature and technology. Here, we reveal a sequential surface-to-bulk-to-surface redistribution of defects in large clusters, whereas defects remain predominantly surface-localised in small crystallites. Using molecular dynamics simulations of colloids with tunable interactions, which serve as molecular-like model systems, we study the spatial distribution of defects and observe pronounced size-dependent defect behaviour during melting. Our results shed light on the role of cluster size in defect formation and melting across systems ranging from atomic clusters to colloidal assemblies.
Developing patient-friendly and non-invasive topical drug delivery systems is essential for improving therapeutic efficacy and patient compliance. In this study, ketotifen (KTF)-loaded microemulgels (μEGs) were formulated using biocompatible ingredients for enhanced topical delivery. Microemulsion (μE) systems composed of castor oil, Emulan EL, isopropanol, and water with varying surfactant/co-surfactant ratios (Smix) were developed to systematically investigate the influence of formulation composition on microstructural characteristics and topical drug delivery performance and subsequently gelatinized using PEG-6000 and Poloxamer 407 to achieve controlled skin permeation. Pseudoternary phase diagram analysis identified optimized formulations containing ∼11% castor oil, ∼14% water, and ∼75% Smix, capable of incorporating ∼2.5 wt% KTF. Conductivity and viscosity analyses confirmed phase transitions from water-in-oil (w/o) to oil-in-water (o/w) systems through a bicontinuous phase. Transmission electron microscopy and dynamic light scattering revealed monodisperse nano-sized droplets with sizes ranging from ∼49–95 nm for μEs and ∼61–120 nm for KTF-loaded μEGs. Ex vivo permeation studies using rabbit skin in a Franz diffusion cell at pH 7.4 demonstrated enhanced permeation, with μEGs achieving >90% drug release after 12 h. The improved performance was attributed to their nanoscale droplet size and higher viscosity, and the combined physicochemical and permeation analyses established a clear relationship between formulation composition, microstructural evolution, and topical permeation behavior. These findings provide mechanistic insight for the rational optimization of μE-based topical drug delivery systems.
Extracellular enzymes from plants and microorganisms drive soil nutrient recycling, yet how mineral interfaces regulate enzyme activity remain unclear. Here, we investigated two extracellular phosphatases, from plant Ipomoea batatas and fungus Aspergillus niger, interacting with quartz, goethite, and illite. Enzyme kinetics, molecular modeling, and infrared spectroscopy were combined to resolve interfacial mechanisms controlling catalysis. For plant phosphatase, despite comparable adsorbed fractions, activity loss was 17% greater on illite than on goethite or quartz. Stronger inhibition by illite was consistent with direct surface interactions that suppressed enzyme flexibility, whereas water-mediated interactions on goethite and quartz caused minor perturbations of catalytic core. For fungal phosphatase, adsorption was up to 3-fold higher on illite than on goethite or quartz, but activity loss differed by only about 10%. Illite promoted rigid β-sheet–rich conformation with reduced α-helix and random-coil content, while weaker binding on goethite and quartz produced transient structural perturbations that caused activity loss.
Cancer remains one of the leading causes of morbidity and mortality worldwide, accounting for nearly 20 million new cases and 10 million deaths annually. Melittin, the principal bioactive peptide of Apis mellifera venom, has attracted considerable interest due to its potent anticancer properties, including membrane disruption, apoptosis induction, and inhibition of tumor growth and metastasis. However, its clinical application is limited by severe hemolytic activity, non-selective cytotoxicity, rapid proteolytic degradation, and a narrow therapeutic window. To address these challenges, lipid vesicle–based nanocarriers such as liposomes, niosomes, and bilosomes have emerged as promising delivery systems. These platforms enhance melittin stability, improve pharmacokinetics, reduce systemic toxicity, and facilitate tumor-targeted delivery. This review summarizes recent advances in melittin-loaded lipid vesicles, highlighting formulation strategies, surface engineering approaches, anticancer mechanisms, and preclinical evidence across various cancers. Lipid vesicle–mediated melittin delivery represents a promising strategy for improving the safety and therapeutic efficacy of peptide-based cancer treatment.
