Nanotechnology, Science and Applications最新文献

Purpose: Small extracellular vesicles (sEVs) are nanoscale biomaterial-like structures involved in intercellular communication and cancer progression. Aberrant surface glycosylation may serve as a diagnostic marker for malignancy. This study aimed to compare the size, glycosylation, and biophysical properties of sEVs secreted by primary and metastatic melanoma cells, and to evaluate a novel analytical technique for glycoprofiling.

Methods: sEVs were isolated from the primary (WM115) and metastatic (WM266-4) melanoma cell lines. Their size and concentration were assessed via Nanoparticle Tracking Analysis (NTA), and exosomal identity was confirmed using Western blotting. Glycosylation profiling was performed using a multimodal strategy: Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), Nanoplasmonic Sensing (NPS), and, for the first time, Flow-Induced Dispersion Analysis (FIDA). Concanavalin A (Con A) was used as the probe for high-mannose glycans.

Results: WM266-4-derived sEVs were significantly larger, whereas WM115 cells secreted more vesicles. Western blotting confirmed the presence of exosomal markers and absence of organelle contaminants. QCM-D and NPS showed stronger Con A binding and higher glycan viscoelasticity index (gVI) in metastatic sEVs, indicating altered glycan architecture. FIDA further confirmed these differences by quantifying a lower dissociation constant (Kd) and multivalent binding behavior in WM266-4-derived sEVs, consistent with a denser glycan coat.

Conclusion: Metastatic melanoma-derived sEVs exhibited distinct Con A-detectable high-mannose glycosylation patterns that may represent malignancy-associated features. This study demonstrates the utility of multimodal nanobiophysical methods, particularly FIDA, as sensitive tools for EV glycoprofiling. While the present findings are based on cell line-derived sEVs, they support the translational potential of glycan-based signatures for future liquid biopsy platforms and expand the analytical capabilities of cancer nanodiagnostics.

Introduction: Glioblastoma (GBM) is a highly heterogeneous and aggressive tumor characterized by rapid growth and therapy resistance. The dynamic interactions of tumor cells with the extracellular matrix (ECM) contribute to treatment inefficacy. While diamond nanoparticles (NDs) are emerging as potential antitumor agents, their mechanisms remain incompletely understood. In this study, we investigated spherical NDs with distinct surface compositions and hydrocolloidal stability and their role in regulating crucial cellular processes in T98G glioblastoma cells.

Methods: Two types of detonation diamond nanoparticles (NDs) were characterized using TEM imaging and hydrocolloidal stability assessment in various diluents. Their effects on T98G glioblastoma cells were examined through SEM imaging, cytotoxicity assays, monitoring of spontaneous and collective migration, and early adhesion examination combined with an extensive integrin-blocking panel. Furthermore, characterization via mass spectrometry provided deeper insight into how physicochemical differences between the two NDs types modulate glioblastoma microenvironment and cell responses.

Results: NDs were observed to be both intensively internalized by cells and bound to cell membrane, influencing cellular interactions with the extracellular environment. NDs significantly reduced T98G glioblastoma cell migration within 48 hours and impaired early adhesion by effectively blocking α/β integrins. Modified NDs (NDM) demonstrated enhanced hydrocolloidal stability and stronger integrin blocking efficiency. Proteomic analysis revealed that NDs downregulated proteins involved in RNA processing, splicing, and translation while upregulating ECM-related proteins, which profile changed depending on the NDs type.

Conclusion: These findings suggest that NDs with distinct surface properties may interact with multiple surface receptors, independently modulate intracellular signaling pathways, and remodel the tumor microenvironment by altering ECM protein composition, positioning them as versatile, multi-targeting agents with antitumor potential.

Ferroptosis, an iron-dependent form of regulated cell death, is increasingly leveraged in nanomedicine to sensitise tumours and overcome drug resistance. Driven by the Fenton reaction, ferroptosis results in lipid peroxidation through elevated intracellular iron levels and excessive production of reactive oxygen species (ROS). In this review, we outline the molecular markers of ferroptosis and define the criteria necessary to attribute ferroptosis induction to nanoparticles (NPs). We emphasise the importance of distinguishing targeted ferroptosis from non-specific ROS-mediated nanotoxicity and other types of programmed cell death. This distinction requires the use of lipophilic radical-trapping antioxidants (eg, ferrostatin-1, liproxstatin-1), iron chelators, and evidence implicating glutathione peroxidase 4 (GPX4) or the system Xc^- antiporter. Morphology is considered supportive but non-diagnostic, requiring converging evidence from both biochemical and genetic sources. We then compare various nanosystems designed to induce ferroptosis, such as iron-based nanoparticles, lipid nanocarriers, light-triggered nanoparticles, and magnetically induced nanocarriers, highlighting mechanistic patterns, efficacy determinants, and common pitfalls that often occur during biological investigations. Finally, we discuss translational challenges, including tumour microenvironment heterogeneity, NP protein corona dynamics, clearance and off-target effects. We aim to provide a framework that links NP design to ferroptotic mechanisms and clinically relevant outcomes, offering clear criteria and priorities for future research.

This review explores the emerging potential of theranostic approaches in the pulmonary delivery of antimicrobial agents, with particular attention to recent FDA warnings concerning inhaled antifungal therapies. Pulmonary infections remain difficult to treat effectively due to the limitations of systemic drug delivery, anatomical and physiological barriers within the lungs, and microbial strategies that promote colonization. Inhaled drug delivery offers a targeted alternative but faces significant challenges, including the inherent variability of lung anatomy, disease-induced pulmonary alterations, and host defence mechanisms. We examine the crucial role of lung imaging in enabling theranostic applications, emphasizing magnetic resonance imaging (MRI) as the most promising modality due to its ability to provide non-invasive, radiation-free, and repeatable assessments of drug deposition. Within this context, the use of superparamagnetic iron oxide nanoparticles (SPIONs) as MRI contrast agents is critically assessed. SPIONs offer a safer alternative to gadolinium-based agents and hold considerable promise for improving the precision of imaging and treatment monitoring in the lungs. The article also outlines the significant regulatory barriers to the development and clinical adoption of inhaled antimicrobial therapies. These include the lack of standardized patient selection criteria, poorly defined clinical endpoints, and the inherent complexity of trial design for heterogeneous patient populations. To address these issues, we propose a conceptual framework for translating inhaled theranostic formulations into personalized antimicrobial therapies. This includes individualized dose adjustments based on imaging data and real-time monitoring of drug concentrations at the infection site. Such a tailored approach could significantly enhance treatment outcomes and meet the urgent clinical need for safer, more effective inhaled antimicrobial treatments.

Background: Vesicular drug delivery systems, including bilosome-based nanoparticles containing bile salts, have revolutionized the field of colloid chemistry, nanomedicine, and nanobiotechnology. Due to their versatility and adaptability to various applications, they have gained considerable attention among researchers, thus offering a promising pathway to achieve effective and targeted delivery of miscellaneous drugs.

Purpose: This study presents a novel class of positively charged bilosomes with surface-associated poly(ethylene glycol) (PEG)-lipid, co-entrapped the anionic xanthene dye (Rose Bengal), and natural carotenoid pigment derived from the mold Blakeslea trispora (astaxanthin), as a safe and effective transdermal drug delivery system.

Methods: Bilosomal nanosystems were prepared using thin film hydration combined with sonication. The physicochemical properties of the vesicles were characterized, including particle size, zeta potential, entrapment efficiency, and morphology. Cellular uptake, cyto- and phototoxicity experiments were investigated in vitro against human melanoma cancer cells.

Results: The multidrug bilosome formulation exhibited a particle size of less than 100 nm and a zeta potential of more than +40 mV, indicating beneficial properties for potential transdermal administration. In vitro biological experiments have shown remarkable antitumor efficacy against human skin epithelial (A375) and malignant (Me45) melanoma cell lines. After irradiating the samples with green light at a wavelength of 520-560 nm (10 J/cm² of total light dose), we observed a significant decrease in mitochondrial metabolic activity, ie, a reduction in cell viability below 30% compared to the control. Higher phototherapeutic activity, in contrast to the administration of non-encapsulated active agents, indicates shared synergistic effects through the simultaneous action of advanced bilosome-derived nanophotosensitizers and phyto-photodynamic therapy.

Conclusion: Our encouraging results provide new potential candidates for preclinical development in innovative photodynamic therapy targeting melanoma and also pave the way for future therapeutic strategies with broad applications in many biological fields.

Purpose: Biofilm-related infections, especially those associated with medical devices like catheters, pose significant clinical challenges due to their resistance to conventional treatments. This study investigates a green chemistry-based approach to synthesize silver nanoparticles (AgNPs) stabilized with trans-cinnamaldehyde (t-CA) and evaluates their potential for combating microbial biofilms and based on novel mechanism of action.

Methods: Silver nanoparticles (t-CA-AgNPs) were synthesized using t-CA as both a reducing and stabilizing agent. The NPs were then thoroughly characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), electron microscopy (TEM, SEM, STEM), and dynamic light scattering (DLS). We evaluated its antimicrobial potential against the most prevalence biofilm-forming pathogens including Pseudomonas aeruginosa, Escherichia coli and Candida albicans using minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) assays. Moreover, we investigated the mechanism of action of t-CA-AgNPs underlying biofilm inhibition. Biofilm formation and structure were verified by SEM imagining.

Results: DLS analysis confirmed that t-CA-AgNPs had an average particle diameter of 2.5 nm, coupled with a notably negative zeta potential (-45 mV), indicative of good colloidal stability. t-CA-AgNPs displayed potent antimicrobial properties, with MIC values ranging from 26 to 412 µg/mL and MBC values from 103 to 825 µg/mL. Biofilm formation inhibitory properties reached 88.74% of inhibition for P. aeruginosa and 70.60% for E. coli. Moreover, we found potent metal ion-chelating capabilities, importantly, in binding and reducing ferrous ions, the crucial factor of biofilm formation. Furthermore, t-CA-AgNPs substantially impaired biofilm development on catheter surfaces, underscoring their robust antibiofilm potential.

Conclusion: Presented here t-CA-AgNPs exhibit significant antimicrobial and antibiofilm activity. By effectively targeting critical elements in biofilm formation, such as ferrous ions, coupled with antimicrobial potential of both active compounds, these green-synthesized NPs have potential applications in significantly improving the safety and effectiveness of medical devices. However, further studies are needed to ensure their efficacy in clinical use.

Introduction: The floating catalyst chemical vapour deposition (FC-CVD) method is widely used for synthesising carbon nanotubes (CNTs), typically with ferrocene as the catalyst. This study explores the use of alternative, nonferrous metallocenes to investigate their impact on carbon nanostructure formation.

Methods: Six metallocenes - ferrocene, cobaltocene, ruthenocene, vanadocene, manganocene, and magnesocene - were tested under comparable FC-CVD conditions. The resulting materials were characterised using scanning electron microscopy (SEM), Raman spectroscopy, and energy-dispersive X-ray spectroscopy (EDS).

Results and discussion: Ferrocene produced vertically aligned CNT carpets with high crystallinity. Cobaltocene and magnesocene also yielded CNTs, though less aligned and more defective. Ruthenocene and vanadocene resulted in disordered graphitic carbon without nanotube morphology, confirmed by the presence of broad D and G bands in Raman spectra. Notably, manganocene catalysed the formation of dendritic structures with oxidised and functionalised surfaces, exhibiting unique morphologies distinct from conventional CNTs.

Conclusion: These results highlight the ability of nonferrous metallocenes to direct the growth of unconventional carbon nanostructures. The findings suggest new possibilities for tailoring nanocarbon morphology through catalyst selection, particularly for applications requiring high surface area or chemical functionality.

Purpose: This study investigated the development and characterization of trans-resveratrol-loaded transfersomes, with and without cholesterol, for potential non-irritating dermal applications.

Methods: Transfersomes were prepared using thin-film hydration combined with probe sonication, incorporating hydrogenated lecithin, cholesterol, and Tween^® 60 in six different ratios. The formulations were characterized for their physicochemical properties, including particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, in vitro release profiles, dermal permeation potential, and safety profile.

Results: All formulations exhibited particle sizes below 150 nm and zeta potentials below -30 mV, indicating favorable characteristics for dermal delivery. Cholesterol incorporation significantly increased particle size and enhanced zeta potential (p<0.05). Formulations containing 3-3.5% w/v hydrogenated lecithin achieved superior entrapment efficiency (>90%) compared to those with lower lecithin content (p<0.05), regardless of cholesterol incorporation. Transfersomes containing cholesterol displayed morphology with well-defined edges compared to cholesterol-free formulations. In vitro release studies revealed distinct release profiles, with cholesterol-free formulations releasing 70-83% of trans-resveratrol over 24 hours, compared to only 0-30% for cholesterol-containing formulations. Strat-M^® membrane-based permeation studies confirmed enhanced trans-resveratrol delivery across all transfersomal systems compared to the saturated solution (p<0.05), though cholesterol showed no significant impact on permeation efficiency. These findings indicate that cholesterol influences release profile but has limited effect on permeation efficiency. Safety assessment using the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay classified the developed transfersomes as weak irritants, indicating their dermal safety. Notably, formulation F3, with a hydrogenated lecithin to cholesterol to Tween 60 ratio of 6:0:4, emerged as the optimal candidate, achieving the highest release rate (80.24% over 24 hours) while maintaining favorable permeation compared to control.

Conclusion: These findings feature the potential of transfersomal systems, particularly cholesterol-free variants, as promising carriers for the effective and safe dermal delivery of trans-resveratrol.

Purpose: Electrospinning enables the formation of nanofibers by elongating a polymer solution droplet in a high-voltage electrostatic field. The drug substance incorporated into nanofibrous matrix exhibits unique dissolution characteristics, modifiable by polymers selection. The physicochemical properties of the drug substance may also influence structural and functional attributes of the nanofibers. This study aimed to produce nanofibers loaded with small-molecule drugs - omeprazole (OMZ) and bisoprolol hemifumarate (BIS) to investigate how drug and polymer properties influence fiber formation and drug release. The effect of compression into minitablets on dissolution parameters was also assessed.

Methods: Ethanolic solutions of Eudragit^® RL (ERL), Eudragit^® RS (ERS), and polyvinylpyrrolidone (PVP) were mixed in 13 combinations. OMZ or BIS was dissolved in each mixture and electrospun. Selected nanofibers were compressed into minitablets. Nanofiber morphology, diameter, drug crystallinity and content uniformity were assessed. Dissolution profiles and release kinetics were evaluated for nanofibers and minitablets.

Results: Nanofibers morphology depended on the API and polymers composition. The BIS fibers were nanosized, while OMZ fibers showed heterogeneous thicknesses ranging from 0.54 µm to 5.7 µm. The drug substances were amorphous in nanofibers. OMZ formulations exhibited a sustained release except OMZ_PVP fibers, which released OMZ immediately. The BIS-loaded nanofibers demonstrated a rapid and nearly complete drug release, except for the BIS_ERL+ERS_7+3 formulation, which exhibited prolonged release. Compression of fibers into minitablets preserved the sustained drug release for both drug substances.

Conclusion: The study proves that nanofibers based on Eudragit RL/RS and PVP can be obtained by the electrospinning method. BIS properties such as good solubility, balanced hydrophobic-lipophilic nature, surface charge, and amorphous form contributed to its rapid release, unlike OMZ.

Background: Ferulic acid (FA) exhibits therapeutic potential for various disorders, but its clinical application is hindered by poor bioavailability and solubility. This study aimed to develop and evaluate FA-loaded lipid nanoparticles (FA-LNPs) as a safe and efficient drug delivery system.

Methods: FA-LNPs were prepared via an optimized active loading method. The Morris water maze test was conducted to evaluate FA efficacy against LPS-induced cognitive impairment in rats. Comprehensive neurotoxicity assessment was performed in three brain regions (striatum, hippocampus, and cerebellum-brain stem) using multiple staining techniques (LFB, GFAP, IBA-1, and Fluoro-Jade) to evaluate myelin integrity, glial activation, and neuronal degeneration. Acute toxicity, pharmacokinetics, and network pharmacology analysis were conducted to assess safety profiles and potential mechanisms.

Results: FA-LNPs were successfully prepared using an optimized active loading method, achieving high drug loading (≥4 mg/mL), superior encapsulation efficiency (EE%) ≥80%, and uniform particle size distribution (<200 nm, PDI=0.053), zeta potential of +5.97 mV (Quality Factor = 1.701), excellent storage stability over two weeks, and was scaled up for batch production. The Morris water maze test revealed an effective FA concentration of 50 mg/kg, with FA-LNPs achieving 46.5 mg/kg through active loading method. Toxicological studies demonstrated favorable safety profiles. Pharmacokinetic analysis showed a prolonged elimination half-life (12.8 ± 1.88 hours) and moderate systemic clearance (0.535 ± 0.0851 L/h/kg). Short-term administration did not elicit significant neuroprotection. Network pharmacology analysis identified 141 potential therapeutic targets and five key proteins (EGFR, ESR1, PTGS2, CTNNB1, and STAT3), with molecular docking confirming favorable binding energies (-7.6 to -5.2 kcal/mol).

Conclusion: FA-LNPs enhanced FA's bioavailability without apparent systemic toxicity or neurotoxicity. While safe for short-term use, longer treatment durations may be necessary to observe potential neuroprotective benefits and toxicity. This study provides a foundation for further investigation of FA-LNPs as a promising drug delivery system for neurological disorders.