Search Results (279)

Nanostructured drug-delivery materials—liposomes, polymeric nanoparticles, dendrimers, and inorganic carriers—have become central to pharmaceutical strategies for crossing the blood–brain barrier (BBB), where most candidate therapeutics fail to reach their targets. Their biological performance hinges on a coupled chain of vascular transport, BBB translocation, tissue diffusion, cellular uptake, and intracellular release, each of which is shaped by the nanocarrier’s size, surface chemistry, charge, and ligand functionalization. Physiologically based pharmacokinetic (PBPK) models describe this chain mechanistically but are limited by parameter uncertainty, simplified representations of the BBB, and coarse regional resolution. Machine learning (ML) can close these gaps by extracting nonlinear structure–transport–exposure relationships from heterogeneous experimental and clinical datasets. This review examines emerging ML–PBPK hybrid frameworks for predicting the brain biodistribution of nanostructured drug carriers. We compare regression, kernel, and deep learning approaches for parameter inference, model correction, and surrogate modeling; assess strategies for feature selection, uncertainty quantification, and interpretability; and discuss documented failure cases that bound the conditions under which these methods can be trusted. The review closes with recommendations on dataset standardization, software platform selection, and the responsible use of generative AI in pharmaceutical modeling, thus providing guidance for translating nanostructured material design into safer, more effective brain-targeted therapies. Full article

Background: Colorectal cancer (CRC) is a major clinical challenge due to high metastasis and therapy resistance. Photodynamic therapy (PDT) offers precise tumor ablation but lacks sustained anti-metastatic activity. Peptidic urokinase-type plasminogen activator (uPA) inhibitors suppress metastasis but suffer from short half-life and poor tumor retention. This study aimed to develop a dual-functional self-assembled nanoplatform integrating PDT and selective uPA inhibition for synergistic CRC treatment. Methods: We designed and synthesized a conjugate by linking pyropheophorbide-a (PPA) with uPA-targeted cyclic peptide IG2, which self-assembled into nanoparticles (PINPs). Physicochemical properties, reactive oxygen species (ROS) generation, and uPA inhibitory activity were characterized. In vitro studies included cellular uptake, cytotoxicity, and invasion assays. In vivo therapeutic efficacy was evaluated in subcutaneous CT26 tumor models and lung metastasis models, with biosafety assessed by body weight monitoring. Results: PINPs exhibited uniform spherical nanostructure, prolonged blood circulation, and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. Under 680 nm irradiation, PINPs generated robust ROS and induced tumor cell apoptosis. PINPs potently inhibited uPA activity and suppressed tumor cell invasion. In vivo, PINPs plus PDT achieved significant tumor growth inhibition (73.6%) and strong anti-metastatic efficacy (60.7%), superior to free IG2. No obvious systemic toxicity was observed. Conclusions: The dual-functional PINPs achieve short-term acute tumor ablation via PDT and sustained anti-metastatic potential via uPA inhibition within the tested observation windows, with favorable biosafety. This carrier-free self-assembly strategy provides proof-of-concept validation and a generalizable design paradigm for developing synergistic anti-metastatic nanotherapeutics against metastatic CRC. Full article

Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer nanostructures containing endogenous lipids, proteins, nucleic acids, and phytochemicals, which have attracted increasing interest as bioinspired carriers for cancer therapy. This review evaluates how plant source, isolation, purification procedures, vesicle composition, cargo-loading strategy, and administration route shape the quality and tumor-delivery performance of PELNs. The available evidence indicates that plant source and processing are major determinants of particle size, purity, surface charge, cargo profile, and biological activity. Ultracentrifugation remains widely used but is limited by contaminant co-isolation and poor scalability, whereas density-gradient purification and size-exclusion chromatography improve purity, and ultrafiltration and tangential flow filtration offer greater potential for large-scale manufacturing. Passive incubation generally preserves vesicle integrity and is most suitable for hydrophobic small molecules, whereas electroporation, sonication, and extrusion can increase cargo loading but may cause aggregation, membrane remodeling, or loss of endogenous components. Preclinical studies suggest that PELNs can exert intrinsic antitumor effects, modulate the tumor microenvironment, improve chemotherapeutic delivery, and help overcome drug resistance. However, evidence for in vivo tumor-targeting remains less robust than evidence for cellular uptake, and direct comparisons with established nanocarriers remain scarce. Clinical translation will require standardized nomenclature and characterization, reproducible manufacturing, quantitative loading and release assays, route-specific biodistribution studies, and repeated-dose safety evaluation. These findings provide a framework for the rational development of PELNs as reproducible tumor-oriented nanocarriers. Full article

Background/Objectives: Plant-mediated silver nanoparticles (AgNPs) are promising components for oral biomaterials because of their antimicrobial potential; however, their biological behavior depends strongly on the phytochemical matrix, physicochemical characteristics, and exposure concentration. This study aimed to evaluate silver nanoparticles formulations synthesized using turmeric powder-derived Curcuma longa ethanolic and aqueous extracts, with emphasis on physicochemical characterization, antibacterial activity against oral-relevant Gram-positive bacteria, cytocompatibility toward human gingival fibroblasts (HGF-1), and acute in ovo vascular compatibility. Methods: AgCUR-EtOH NPs and AgCUR-H₂O NPs were synthesized using CUR-EtOH and CUR-H₂O extracts as reducing and stabilizing matrices. The resulting formulations were characterized by UV–visible spectroscopy (UV-Vis), dynamic light scattering (DLS), zeta-potential analysis, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Streptococcus mutans, Streptococcus oralis, and Staphylococcus aureus. Cytocompatibility was evaluated in HGF-1 human gingival fibroblasts after 24 h exposure to 1–10 µg/mL using complementary viability, lysosomal, mitochondrial, and fluorescence-based assays. Acute vascular irritation was assessed using the hen’s egg test–chorioallantoic membrane (HET-CAM) assay. Results: Both formulations exhibited broad, polydisperse hydrodynamic distributions and negative apparent zeta potentials. AgCUR-H₂O NPs showed a lower Z-average diameter than AgCUR-EtOH NPs under their respective solvent-specific measurement conditions. XRD pattern revealed heterogeneous crystalline compositions dominated by residual AgNO₃, together with weaker contributions consistent with metallic Ag and a possible minor oxidized silver phase. FTIR spectra demonstrated extract-derived organic functional groups and prominent nitrate-associated bands. TEM/EDX confirmed Ag-containing nanostructures with approximate size ranges of 15–175 nm for AgCUR-EtOH NPs and 15–150 nm for AgCUR-H₂O NPs. S. mutans was the most susceptible microorganism, with MIC values of 9 and 7 µg/mL and MBC values of 88 and 62 µg/mL for AgCUR-EtOH NPs and AgCUR-H₂O NPs, respectively. AgCUR-H₂O NPs consistently showed lower MIC and MBC values against all tested strains, but also produced a more pronounced concentration-dependent reduction in HGF-1 viability. At 10 µg/mL, cell viability was 71.88% for AgCUR-EtOH NPs and 52.14% for AgCUR-H₂O NPs. Both formulations showed low acute irritation potential in ovo, with irritation scores of 1.06 and 0.69, respectively. Conclusions: The two CUR-AgNP formulations exhibited distinct physicochemical, antibacterial, and cellular response profiles under the tested conditions. At equivalent concentrations expressed as total dried formulation mass, AgCUR-H₂O NPs yielded lower MIC and MBC values against the tested bacterial strains, whereas AgCUR-EtOH NPs produced a less pronounced reduction in HGF-1 viability. Because the powders were not quantitatively normalized for total silver, extract-derived organic fraction, or residual precursor content, these differences cannot be attributed exclusively to nanoparticle properties or to the extraction solvent and should not be interpreted as evidence of the intrinsic superiority of either formulation. Both formulations showed low acute vascular irritation. Further quantitative compositional, silver-release, and biofilm assessments are required before incorporation into oral biomaterial platforms. Full article

RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines. Full article

Polyetheretherketone (PEEK) has emerged as a promising biomaterial for orthopedic and craniofacial implants due to its favorable mechanical properties and fatigue resistance; however, its inherent chemical inertness limits effective osseointegration. In this study, femtosecond laser surface modification is explored as a strategy to enhance the bioactivity of PEEK. Based on a previously performed parametric study, controlled micro- and nanoscale surface textures were fabricated using femtosecond laser processing, enabling precise tuning of surface roughness and wettability without the need for additional chemical treatment. The modified surfaces were systematically characterized in terms of morphology, composition, and topography using scanning electron microscopy (SEM), 3D profilometry, and water contact angle measurements. Four optimized femtosecond laser-generated surface architectures were selected for the present investigation and comprehensively characterized, followed by in vitro evaluation of dental pulp stem cell adhesion, morphology, and proliferation. The results indicate that laser-induced micro/nanostructuring enhances the surface properties of PEEK, while supporting cellular attachment and favorable cell–surface interaction. Differences in the biological response were observed among the optimized laser-textured surfaces. These findings highlight the feasibility of femtosecond laser texturing as a clean, reproducible, and scalable approach for the development of next-generation, personalized orthopedic implants. Full article

Recent advances in vaccinology have accelerated the shift from conventional live-attenuated and inactivated vaccines toward subunit and nucleic acid-based platforms. Although these next-generation vaccines offer improved safety, rapid adaptability, and manufacturing flexibility, their relatively low intrinsic immunogenicity often requires efficient adjuvants and delivery systems. Nanoparticle-based vaccine platforms have therefore emerged as versatile tools capable of protecting antigens, improving targeted delivery, and modulating both innate and adaptive immune responses. This review summarizes the major classes of nanovaccine platforms, including lipid and polymeric nanoparticles, self-assembling protein nanostructures such as virus-like particles and ferritin nanocages, saponin-based self-assembling complexes, and inorganic nanomaterials. Particular attention is given to how vaccine performance is determined not only by material composition but also by nanoparticle physicochemical properties, biodistribution, cellular uptake, and mechanisms of immune activation. We further discuss the major challenges limiting clinical translation, including scalable manufacturing, safety evaluation, quality control, regulatory requirements, and long-term biocompatibility. Finally, emerging strategies involving hybrid and personalized nanovaccine platforms are highlighted, illustrating how nanotechnology and immunoengineering are transforming vaccine development for both prophylactic and therapeutic applications. Full article

Background: Streptococcus mutans (S. mutans) plays a major role in dental biofilm-related infections and contributes to antimicrobial resistance. Therefore, the development of biocompatible nanomaterials with antibacterial, antibiofilm, and regenerative properties is important for dental applications. Methods: In this study, hyaluronic acid and clove extract were used as natural precursors to synthesize hyaluronic acid-clove carbon dots (HCCDs) through a hydrothermal method. The synthesized HCCDs were characterized by XRD, FTIR, TEM, SEM, SAED and EDAX analysis. The antibacterial and antibiofilm activities against S. mutans were tested. Cell viability tests, AO/PI staining, morphological observation and wound-healing assays were used to evaluate cytocompatibility in MG-63 cells. Results: A broad peak (23.449) observed from XRD coincided with an amorphous graphitic carbon structure. TEM images showed the presence of a spherical nanostructure with an average size of 4 ± 2 nm. The FTIR result verified the presence of hydroxyl, carbonyl and oxygen-containing functional groups on the HCCD surface. Their synthesized HCCDs exhibited noteworthy antibacterial and antibiofilm activity with an MIC of 62.5 µg/mL against the S. mutans. Low toxicity toward MG-63 cells was observed, with 86% cell viability at 200 µg/mL in the cytocompatibility study. Additional good cellular compatibility was confirmed using AO/PI staining and morphological analysis. Furthermore, normal cell migration was observed, as wound healing assays showed no significant difference in closure between the treated and control groups. Conclusion: HCCDs exhibited antibacterial, antibiofilm, biocompatible, and wound-healing properties, highlighting their potential for dental nanomedicine and the treatment of oral biofilm-associated infections. Full article

Tea tree essential oil (TTO), extracted from Melaleuca alternifolia, is a terpene-rich botanical antimicrobial with demonstrated broad-spectrum activity against foodborne pathogens and spoilage microorganisms. Its bioactivity is principally attributed to oxygenated monoterpenes, most notably including terpinen-4-ol, γ-terpinene, and α-terpinene, whose structure–activity relationships govern interactions with microbial membranes and intracellular targets. This review provides a comprehensive, mechanistically grounded analysis of TTO as a sustainable antimicrobial platform for food preservation applications. The physicochemical determinants of TTO performance are critically assessed, encompassing chemotype-dependent compositional variability, hydrophobicity, limited aqueous solubility, and oxidative instability, with emphasis on how these properties constrain efficacy in complex food matrices. Antimicrobial mechanisms are systematically examined, including membrane permeabilization, disruption of cellular homeostasis, oxidative stress induction, and quorum-sensing interference. Focus is placed on nanostructured delivery systems, including nanoemulsions, biopolymer-based encapsulants, and hybrid nanocomposites, that improve physicochemical stability, modulate release kinetics, and potentiate antimicrobial activity. The integration of these engineered formulations into edible coatings, active packaging, and sanitation protocols across fresh produce, meat, and dairy systems is evaluated in the context of practical food safety applications. Translational limitations are addressed, including volatility, sensory incompatibility, regulatory constraints, and concentration-dependent cytotoxicity considerations. Collectively, this review positions TTO-based nanoformulations as a scientifically promising and technologically scalable approach to next-generation food preservation, while identifying critical gaps that must be resolved to support regulatory acceptance and commercial implementation. Full article

Hydrogen peroxide (H₂O₂) is a key reactive oxygen species involved in both cellular signaling and oxidative stress, making its reliable detection essential in biological and environmental systems. Electrochemical sensing has emerged as a promising approach for H₂O₂ monitoring due to its high sensitivity, rapid response, and suitability for in situ analysis. This review provides a comprehensive overview of nanostructured metal oxide electrodes for non-enzymatic electrochemical detection of H₂O₂. The effects of material composition, nanostructure morphology, and synthesis strategies (particularly hydrothermal methods) on sensor performance are critically discussed. Special attention is given to our previously reported studies, enabling a consistent comparison of structure–property relationships under similar experimental conditions. Furthermore, the application of these sensors in plant stress analysis is examined, including both the monitoring of oxidative stress and the evaluation of stress mitigation strategies using metal oxide nanoparticles. The role of nanoparticles as reactive oxygen species scavengers and enhancers of plant antioxidant systems is highlighted, demonstrating their ability to reduce H₂O₂ levels and improve plant physiological status under adverse environmental conditions. Overall, this work emphasizes the dual functionality of nanostructured materials as both sensing platforms and active agents for stress mitigation, highlighting their potential in agricultural and environmental applications. Full article

Modern cell imaging is increasingly evolving toward high-content, label-free, and spectrally rich analytical approaches capable of resolving biochemical heterogeneity at cellular and subcellular levels. Raman microspectroscopy (µRS) and surface-enhanced Raman scattering (SERS) provide molecularly specific vibrational fingerprints with minimal photobleaching and high multiplexing capability, making them attractive tools for biomedical imaging and cellular analysis. However, broader implementation remains limited by weak intrinsic signals, insufficient targeting specificity, and limited control over nanoscale sensing environments in complex biological systems. Metal–organic framework (MOF) nanoparticles have recently emerged as promising platforms to address these challenges by offering porous, chemically tunable, and structurally well-defined scaffolds for Raman- and SERS-active nanostructures. Their high stability and favourable biocompatibility further support integration into biological applications. This review summarizes recent advances in MOF-assisted µRS and SERS across chemical sensing, bioanalytical detection, and biomedical diagnostics, with particular emphasis on cellular and subcellular imaging. Unlike previous reviews focused primarily on sensing performance, this work highlights the emerging role of MOF-SERS systems in high-content cellular imaging and evaluates their translation toward biologically relevant environments. Key design strategies and current challenges are critically discussed. Full article

Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol biosynthetic pathway, biofilm-associated tolerance, and extensive genomic plasticity. The growing prevalence of antifungal resistance and the limited availability of effective therapeutic options highlight the urgent need to strengthen epidemiological surveillance and accelerate research into innovative therapeutic strategies. In this review, we discuss the potential of lipid-based drug delivery systems (LDDSs) as a versatile strategy to optimize antifungal administration and overcome resistance mechanisms. Liposomes (LPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoparticles (LNPs) offer high biocompatibility, efficient encapsulation of hydrophobic compounds, structural stability, and controlled drug release. Their nanoscale properties facilitate penetration into biofilms, promote intracellular uptake, and reduce the impact of efflux-mediated drug extrusion, thereby improving cellular penetration and circumventing resistance pathways. In addition, LDDSs increase bioavailability, reduce toxicity, and promote drug accumulation within poorly accessible tissue compartments. Overall, LDDSs represent a promising approach to expand the therapeutic arsenal against both superficial and invasive fungal infections, particularly those caused by multidrug-resistant pathogens. Full article

The objective of this study was to compare the protective effects of native and nanostructured quercetin on the initiation of oxidative stress in human keratinocytes exposed to tert-butyl hydroperoxide (tBHP). Quercetin was encapsulated within gelatin-based nanocontainers, forming nanoparticles with diameters ranging from 140 to 180 nm. Two formulations were prepared: uncoated gelatin nanoparticles (NP1) and gelatin nanoparticles coated with a shell composed of dextran sulfate and a chitosan–dextran copolymer (NP2). Cell viability was assessed using PrestoBlue™ reagent. Apoptotic and necrotic cell populations were identified via flow cytometry using an Annexin V-FITC/PI staining kit. DNA damage was evaluated using the comet assay. The results demonstrate that gelatin nanoparticles effectively encapsulate quercetin, and the nanostructured form enables its application in aqueous suspensions without compromising its antioxidant, gene-protective, and cytoprotective effects under conditions of cellular oxidative stress. These findings suggest that gelatin nanoparticles are suitable carriers for quercetin, owing to their high aqueous solubility, which may improve its potential for oral or topical delivery. Full article

Acute kidney injury (AKI) presents a critical clinical challenge due to its rapid progression and lack of effective targeted therapies. The herbal combination of rhubarb and Salvia miltiorrhiza, a cornerstone of Traditional Chinese Medicine (TCM) for renal protection, shows promise, yet its bioactive components and mode of action remain incompletely understood. This study identifies and characterizes inherent nanoscale entities from this herbal pair as a novel nanotherapeutic platform. Self-assembled nanoparticles (designated RSNPs) were isolated from the ethanol extract via differential centrifugation. Comprehensive characterization revealed that RSNPs form stable nanostructures through spontaneous self-assembly, primarily driven by supramolecular interactions (e.g., π-π stacking and hydrogen bonding). UPLC-MS/MS quantification confirmed the co-assembly of multiple bioactive constituents within RSNPs. Network pharmacology and molecular docking initially predicted their synergistic action on AKI-related pathways. In a cisplatin-induced murine AKI model, RSNP administration markedly attenuated renal dysfunction and histopathological damage, mechanistically linked to the mitigation of oxidative stress (e.g., decreased MDA and increased SOD) and inflammation (e.g., downregulated TNF-α and IL-6). In vitro, RSNPs demonstrated enhanced cellular internalization and superior cytoprotection against cisplatin toxicity in renal tubular epithelial cells, significantly reducing apoptosis. These findings unveil that the therapeutic efficacy of the Rheum palmatum L.–Salvia miltiorrhiza Bunge pair is intrinsically embedded within its nanoscale architecture. RSNPs represent a new class of TCM-derived nanotherapeutics with a well-defined material basis and multimodal mechanisms, offering a promising strategy for AKI treatment. Full article

Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine’s potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development. Full article