Search Results (471)

Currently, single-modal tumor therapy has significant limitations, while multi-modal combination therapy can overcome this bottleneck and open up new pathways for enhancing the efficacy of tumor therapy. However, it is still difficult to design a functionalized nanocarrier that can simultaneously mediate multiple therapeutic approaches. To tackle this challenge, we developed a multifunctional nano-codelivery system with glucose oxidase (GOx) loaded inside iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8), abbreviated as GFZ. This system effectively integrates the synergy and complementarity between ferroptosis therapy and starvation therapy (STT). Herein, GFZ innovatively combines the pH sensitivity of the ZIF-8 skeleton with the EPR effect of nanoparticles to achieve on-demand triggered release, significantly improving the accuracy of tumor targeting. Furthermore, GOx-mediated STT effectively alleviates the insufficiency of endogenous H₂O₂ during the ferroptosis process, thereby enhancing and synergizing with ferroptosis therapy. Experiments demonstrated both in vitro and in vivo that GFZ activates antitumor cascade reactions, inhibits tumor recurrence and metastasis, and exhibits excellent biocompatibility. Consequently, given its remarkable potential, GFZ is poised to emerge as a new mode of nano-delivery platform. Full article

This study describes the development of an electrochemical sensor for quantitatively measuring acetaminophen (ACOP) in drug tablets. The sensor design is based on the modification of glassy carbon electrode (GCE) using zinc oxide nanoparticles (ZnONPs) embedded in a naturally occurring clay matrix (Sa) functionalized with phenylalanine (Phe). To ensure that the ZnONPs are homogeneously dispersed on the clay surface, the nanocomposite was synthesized using an impregnation approach and low-temperature heat treatment. The amino acid promotes specific interactions with ACOP through hydrogen bonding and π-π stacking, acting as both a stabilizing agent and a molecular recognition moiety. FTIR, UV-Vis, XRD, and FESEM/EDX mapping were employed to fully characterize the developed material (ZnONPs-Sa/Phe). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used for the electrochemical determination of ACOP using the modified electrode GCE/ZnONPs-Sa/Phe. Parameters susceptible to affecting the sensitivity of the developed sensor were optimized, revealing that 5 µL of the suspension ZnONPs-Sa/Phe immobilized on GCE was ideal for the sensing of ACOP in a phosphate buffer solution at pH 2.0. The calibration curve obtained by plotting peak current intensity against ACOP concentration exhibited linear behavior within the concentration range between 0.02 µM and 0.28 µM, enabling determination of the limits of detection (LOD) and quantitation (LOQ) at 8.54 × 10⁻⁹ M and 2.84 × 10⁻⁸ M, respectively. The reproducibility, stability, and selectivity of the sensor were evaluated, followed by its application to the nano-sensing of ACOP in Africure and Doliprane tablets, yielding satisfactory results. The simplicity, affordability, and high analytical sensitivity of the developed sensor make this sensing platform a promising tool for pharmaceutical quality control applications. Full article

A dual-mode electrical–optical nanocomposite hydrogel is developed by integrating carboxyl-modified upconversion nanoparticles (UCNPs-COOH) and quaternized chitosan (CQAS) into a polyacrylamide (PAAm) covalent network. The hydrogel exhibits high optical transparency (>90% in the visible region), excellent mechanical properties (fracture strain of 1742%, tensile strength of 0.85 MPa, toughness of 6.57 MJ/m³), and robust adhesion to various substrates. The synergistic covalent–noncovalent hybrid network enables efficient energy dissipation, while CQAS-enhanced dispersion of UCNPs significantly improves upconversion luminescence intensity and stability, as evidenced by prolonged fluorescence lifetime from 0.564 ms to 0.691 ms at 539 nm. Leveraging distinct electrical and optical signal transduction pathways, the hydrogel functions as a highly sensitive resistive strain sensor with multistage gauge factors up to 13.85 and excellent cyclic stability over 1200 loading–unloading cycles at 100% strain for human motion monitoring. It also serves as a ratiometric optical pH sensor over a broad range (pH 1–13) based on phenolphthalein-sensitized upconversion luminescence, with excellent repeatability. By integrating real-time resistance responses with optical readouts within a single soft material, this work demonstrates a reliable dual-mode sensing strategy for simultaneous mechanical and chemical monitoring, holding promise for wearable electronics, smart healthcare, and environment-responsive sensing systems. Full article

Background/Objectives: Jaw osteomyelitis (OM) is a refractory purulent inflammation caused by bacterial infection, characterized by persistent infection, excessive bone resorption, and resultant bone defects. Currently, mainstream therapies for jaw OM struggle to eradicate persistent infections, avoid antibiotic resistance, and repair infected bone defects, posing a critical challenge in clinical practice. Methods: Herein, the Fe₃O₄@ZIF-8 core–shell nanoparticles (NPs) platform designed for jaw OM treatment consisted of Fe₃O₄ as the core and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Results: The core–shell platform not only integrated the pH-responsive degradation capability of ZIF-8 but also retained the superparamagnetism of Fe₃O₄ NPs. In the acidic, infectious microenvironment, Fe₃O₄@ZIF-8 NPs underwent continuous degradation, releasing Zn²⁺, thereby conferring potent antibacterial activity. The specific antibacterial mechanism of the nanoparticles lies in the fact that high concentrations of Zn²⁺ directly disrupted bacterial cell membranes and inhibited the bacterial heat shock response. This dysregulates bacterial proteostasis, rendering the bacteria more sensitive to external adverse stresses, ultimately leading to bacterial death. With ZIF-8 framework degradation, the encapsulated Fe₃O₄ NPs were released. Under static magnetic field (SMF) synergy, Fe₃O₄ NPs collaborated with Zn²⁺ to promote bone regeneration and repair infected bone defects in jaw OM lesions. Conclusions: As a multifunctional core–shell platform, Fe₃O₄@ZIF-8 NPs meet the dual clinical needs of antibiosis and osteogenesis, offering a promising translational strategy for jaw OM therapy. Full article

In this work, we designed non-viral gene delivery vector systems based on three poly(2-ethyl-2-oxazoline)-ran-poly[2-(3-butenyl)-2-oxazoline] copolymers functionalized by primary, secondary, and tertiary amino groups. The impact of copolymer structure and composition was sought through the examination of basic physicochemical and biological parameters. The complexation ability of copolymers with plasmid DNA was studied by ethidium bromide quenching assay. The polyplex particles size and ζ-potential were determined by dynamic and electrophoretic light scattering. The release ability of copolymers was assessed by competitive displacement of DNA using dextran sulfate. The biological performance of amino-functionalized poly(2-ethyl-2-oxazoline)-ran-poly[2-(3-butenyl)-2-oxazoline] based gene delivery systems was evaluated, and their behavior under various environmental conditions, such as pH and ionic strength, was investigated. Cytotoxicity was assessed in two human lung-derived cell lines, and the ability of the copolymers to mediate plasmid DNA delivery and expression was examined. The resulting polyplex nanoparticles exhibited the ability to release DNA molecules and sensitivity to alterations in pH and ionic strength. All systems showed high biocompatibility and were able to mediate plasmid DNA delivery, resulting in detectable EGFP expression in vitro. The vector properties were found to be driven by a multifactorial interplay among hydrophobic character, thermoresponsive behavior, polymer mobility, charge accessibility, intracellular environmental responsiveness, secondary structure effects, etc. The copolymer bearing primary amino groups displayed a distinct balance between DNA binding and release, characterized by moderate complex stability and enhanced sensitivity to environmental changes. These findings provide mechanistic insight into how amino functionality and polymer structure influence the structure–property–behavior relationships of polyoxazoline-based non-viral gene delivery systems. Full article

Background: The process of healing skin wounds frequently faces obstacles due to inadequate repair. Even though recombinant Epidermal Growth Factor (EGF) is a significant therapeutic agent, its short half-life and instability limit its clinical application. The study’s objective was to establish a lipid nanoparticle (LNP) delivery method for efficiently transporting EGF mRNA, with the goal of achieving sustained local protein expression to aid in wound healing. Methods: EGF mRNA was produced through in vitro transcription and enclosed in pH-sensitive LNPs using microfluidic techniques. The LNP-mRNAEGF’s physicochemical attributes, stability, and biocompatibility were assessed. Its effects on the proliferation and migration of HaCaT cells and on EGF expression were assessed in vitro. The therapeutic effectiveness was assessed using a mouse model with full-thickness skin defects and compared to control groups (saline, empty LNP, recombinant EGF). The study analyzed wound closure rate, histology, immunofluorescence, and systemic safety. Results: The LNP-mRNA_EGF formulation showed a spherical shape and demonstrated good stability. In vitro, it showed excellent biocompatibility, facilitated prolonged EGF expression in HaCaT cells depending on the dose for more than 72 h, and greatly enhanced cell proliferation and migration. In vivo, a single dose of LNP-mRNA_EGF greatly sped up wound healing, almost completely closing the wound by day 10, and was much more effective than all control groups. Histological and immunofluorescence analyses revealed enhanced re-epithelialization, significantly increased and optimized collagen I/III deposition, and an upregulated expression of EGF and E-cadherin. Moreover, no significant toxicity was found in the systemic safety assessment. Conclusions: The LNP-based EGF mRNA delivery platform enables efficient and sustained local protein expression via a single administration. It offers a promising translational strategy for protein replacement therapy in skin repair by significantly accelerating wound healing through enhanced re-epithelialization and optimized collagen remodeling. Full article

Cancer is one of the leading causes of mortality worldwide, with breast and colon cancers being among the most common neoplasms in men and women, respectively. Despite significant advancements in treatment, there is a pressing need to enhance specificity and reduce systemic side effects. Importantly, a distinctive feature of cancer cells is their acidic extracellular environment, which profoundly influences cancer progression. In this study, we evaluated the anticancer activity of a pH-sensitive nanocomposite based on silver nanoparticles and pegylated carboxymethyl chitosan (AgNPs-CMC-PEG) in breast cancer (MCF-7) and colon cancer (HCT 116) cell lines. To achieve this, we synthesized and characterized the nanocomposite using UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (STEM-in-SEM). Furthermore, we assessed cytotoxic effects, apoptosis, and reactive oxygen species (ROS) generation using MTT, DAPI, and H2DCFDA assays. Additionally, we analyzed the expression of DNA methyltransferases (DNMT3a) and histone acetyltransferases (MYST4, GCN5) at the mRNA level using RT-qPCR, along with the acetylation and methylation of H3K9ac and H3K9me2 through Western blot analysis. The synthesized nanocomposite demonstrated an average hydrodynamic diameter of approximately 175.4 nm. In contrast, STEM-in-SEM analyses revealed well-dispersed nanoparticles with an average core size of about 14 nm. Additionally, Fourier-transform infrared (FTIR) spectroscopy verified the successful surface functionalization of the nanocomposite with polyethylene glycol (PEG), indicating effective conjugation and structural stability. The nanocomposite exhibited a pH and concentration dependent cytotoxic effect, with enhanced activity observed at an acidic pH 6.5 and at concentrations of 150 µg/ml, 75 µg/ml, and 37.5 µg/ml for both cell lines. Notably, the nanocomposite preferentially induced apoptosis accompanied by ROS generation. Moreover, expression analysis revealed a decrease in H3K9me2 and H3K9ac in both cell lines, with a more pronounced effect in MCF-7 at an acidic pH. Furthermore, the expression of DNMT3a at the mRNA level significantly decreased, particularly at acidic pH. Regarding histone acetyltransferases, GCN5 expression decreased in the HCT 116 line, while MYST4 expression increased in the MCF-7 line. These findings demonstrate that the AgNPs-CMC-PEG nanocomposite has therapeutic potential as a pH-responsive nanocomposite, capable of inducing significant cytotoxic effects and altering epigenetic markers, particularly under the acidic conditions of the tumor microenvironment. Overall, this study highlights the advantages of utilizing pH-sensitive materials in cancer therapy, paving the way for more effective and targeted treatment strategies. Full article

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Background: Oral insulin improves compliance and convenience in patients with diabetes who require regular needle injections. However, the clinical application of oral insulin preparations has been limited due to instability and inefficient permeation through the gastrointestinal tract. In this study, a novel cationic polysaccharide nanodrug delivery platform was designed for efficient oral insulin delivery. Methods: The innovative thiolated trimethyl chitosan-grafted β-cyclodextrin (NCT) was synthesized by utilizing N-trimethyl chitosan (TMC) as the polymer backbone. This involved modifying TMC with thiol group-containing N-acetylcysteine and carboxymethyl-β-cyclodextrin that possesses hydrophobic cavities via an amide condensation reaction. Subsequently, this polymer was employed to construct the NCT nanoparticle system using an ionic cross-linking method. The physicochemical properties of the NCT nanoparticles were systematically analyzed, and their therapeutic efficacy was comprehensively evaluated in streptozotocin (STZ)-induced animal models. Results: The NCT nanoparticles demonstrated mucus adhesion, permeability, and pH sensitivity, which facilitated a slow and controlled release within the gastrointestinal microenvironment due to both ionic electrostatic interactions and disulfide bonding interactions. The experiments revealed in vivo that insulin/NCT nanoparticles extended the retention time of insulin in the small intestine. Blood glucose levels decreased to approximately 39% of the initial level at 5 h post-administration while exhibiting smooth hypoglycemic efficacy. Simultaneously, insulin bioavailability increased to 12.58%. Conclusions: The NCT nanoparticles effectively protect insulin from degradation in the gastrointestinal microenvironment while overcoming intestinal barriers, thereby providing a promising approach to oral biomolecule delivery. Full article

Background/Objectives: Cancer is a major health concern involving abnormal cell growth. Combining anticancer agents can enhance efficacy and overcome resistance by targeting multiple pathways and creating synergistic effects. Methods: This study used in silico approaches to evaluate the physicochemical and pharmacokinetic profiles of the innovative organoselenium nucleoside analog Di3a, followed by the design of two nanocarriers. Di3a-loaded PLGA nanocapsules and nanostructured lipid carriers based on compritol were prepared and evaluated alone and combined with doxorubicin (DOX) and docetaxel (DTX) for a synergistic effect. Results: Di3a subtly violated some of Lipinski’s rules, but still showed suitable pharmacokinetic properties. Both nanoparticles presented nanometric size, negative zeta potential and polydispersity index values < 0.20. Hemolysis assay suggested a pH-dependent pattern conferred by the surfactant 77KL, and evidenced the biocompatibility of the formulations, aligning with the results observed in the nontumor L929 cell line. The lack of drug release studies under varying pH conditions constitutes a limitation and warrants further investigation to validate the pH-responsive properties of the nanocarriers. MTT assay revealed that both formulations exhibited significant cytotoxic effects in the A549 cell line. However, neither formulation exhibited marked toxicity toward NCI/ADR-RES, a resistant tumor cell line. Conversely, when combined with DOX or DTX, the treatments were able to sensitize these resistant cells, achieving expressive synergistic antitumor activity. Conclusions: Despite the limitations in the in silico studies, the study highlights the potential of combining the proposed nanocarriers with conventional antitumor drugs to sensitize multidrug-resistant cancer cells and emphasizes the safety of the developed nanoformulations. Full article

Zearalenone (ZEN), a stable mycotoxin with estrogenic activity produced by various Fusarium species, poses a serious food safety risk. To facilitate the rapid, sensitive, on-site detection of ZEN in maize and ensure consumer dietary safety, a colloidal gold immunochromatographic assay (CG-ICA) based on a monoclonal antibody was established. ZEN was converted via oxime derivatization into hapten ZAN-O, which was conjugated to a carrier protein to prepare an immunogen for producing a highly specific and sensitive monoclonal antibody. Then, the antibody was conjugated into colloidal gold nanoparticles (AuNPs) and used as capture bioprobes of the CG-ICA test strip. The highly sensitive and specific detection platform was established through systematic optimization of pH value, coating antigen concentration, antibody-labeling dosage, incubation time, and strip assembly conditions. Under optimized conditions, the strip exhibited a detection limit of 11.79 pg/mL and an IC₅₀ of 99.06 pg/mL, with a linear detection range of 13.40–732.48 pg/mL. In addition, the anti-interference capability assay demonstrated that the developed test strip possessed excellent specificity. In spiked maize samples, the CG-ICA test strip demonstrated recoveries ranging from 85.36% to 98.86%, with relative standard deviations (RSDs) below 10%. Thus, the CG-ICA strip provides a rapid, sensitive, and robust on-site tool for ZEN screening in maize, and can be adapted to other hazards by simply switching the antibody. Full article

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumour with limited treatment options and a poor prognosis. Therapeutic failure is driven by multiple barriers, including the blood–brain barrier (BBB), the tumour microenvironment (TME), and intratumoural heterogeneity. Conventional delivery systems often fail to achieve sufficient drug accumulation or controlled release within the tumour. In this review, we outline a theoretical framework for the design of ligand-functionalised magnetic lipid nanoparticles (MF-R-LNs), a multifunctional nanoplatform that integrates active targeting, stimuli-responsive drug release, and external magnetic-field control. The proposed MF-R-LNs incorporate superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic guidance and hyperthermia; polyethylene glycol (PEG) for extended circulation; and surface ligands such as peptides, antibodies, or aptamers to target GBM-specific receptors including epidermal growth factor receptor (EGFR), Interleukin-13 receptor alpha-2 (IL-13Rα2), and integrins. Triggered release mechanisms such as pH-sensitive lipids, redox cleavable linkers, and enzyme-responsive coatings enable selective drug release within the TME. Magnetic hyperthermia serves as both a therapeutic modality and a remote trigger to enhance release and tumour penetration. This modular design offers a theoretically robust strategy to overcome the key physiological and therapeutic barriers in GBM. We discuss the rationale behind each design feature, explore potential synergies, and highlight translational challenges such as tumour heterogeneity, manufacturing complexity, and safety concerns. Despite encouraging preclinical evidence, clinical translation faces substantial hurdles, notably patient-specific heterogeneity and scalable GMP manufacturing/characterisation of multi-component nanoplatforms. While preclinical validation remains necessary, this framework may inform future efforts to develop spatiotemporally controlled, multifunctional therapeutics for glioblastoma. This manuscript is a conceptual framework review that synthesises current strategies into actionable guidance for designing and reporting MF-R-LNs for GBM. Full article

Background: Breast cancer remains one of the most prevalent and lethal malignancies worldwide. Although doxorubicin (DOX) is widely used as a first-line chemotherapeutic agent, its clinical utility is constrained by dose-limiting cardiotoxicity and systemic adverse effects. Nanoparticulate drug delivery systems have therefore attracted attention for improving DOX stability, biocompatibility, and tumor selectivity. In this study, we explored sterosomes—simple non-phospholipid nanocarriers composed of cholesterol and palmitic acid—as an alternative DOX delivery platform with pH-responsive properties. Methods: DOX-loaded sterosomes (DOX-STs) were prepared using cholesterol and palmitic acid to impart acid-sensitive behavior. The nanocarriers were systematically evaluated through particle characterization, physicochemical stability assessment, in vitro pH-dependent drug release, and cellular uptake studies. Furthermore, therapeutic efficacy and systemic safety were investigated in an MDA-MB-231 breast cancer xenograft mouse model. Results: DOX-STs exhibited particle sizes below 100 nm, high encapsulation efficiency, and excellent colloidal stability for 28 days. The sterosomes demonstrated accelerated DOX release under acidic conditions relative to physiological pH, consistent with their pH-responsive design. Enhanced cellular uptake was observed in both MCF-7 and MDA-MB-231 cells. In vivo, DOX-ST treatment resulted in significant tumor growth suppression and prolonged survival without notable body weight loss, indicating reduced systemic toxicity compared to free DOX. Conclusions: This study presents a simple sterosome-based nanocarrier system that achieves pH-responsive DOX release and enhanced antitumor efficacy while minimizing toxicity. These findings highlight the potential of sterosomes as a translatable nanomedicine platform for breast cancer therapy. Full article

Plasma cell myeloma (PCM) is classified as a blood cancer and is characterized by the abnormal proliferation of plasma cells in the bone marrow and the excessive production of monoclonal immunoglobulins, which lead to permanent damage to vital organs. Although treatment strategies have improved with the development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), PCM remains an incurable disease due to its molecular heterogeneity and the development of drug resistance. In this review, we discuss the biochemical and molecular foundations underlying the diagnosis and treatment of PCM, emphasizing both traditional and advanced approaches. Classical methods such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) determination are highlighted alongside their integration with highly sensitive techniques like mass spectrometry (MS) and next-generation sequencing (NGS). Special attention is given to nanotechnology-based systems, including liposomes, polymeric nanoparticles (NPs), dendrimers, and hybrid nanocapsules, which enable controlled drug release, targeted delivery, and the minimization of systemic toxicity. Increasingly, nanomaterials are being shown to greatly enhance the biodistribution and pharmacokinetics of anticancer drugs, leading to improved therapeutic effects and escaping resistance mechanisms by employing multifunctional strategies that include dual drug co-encapsulation, pH-sensitive release and theranostic applications. Furthermore, the integration of nanotechnology with immunotherapy platforms represents a paradigm shift toward precision and personalized medicine for the treatment of PCM. Overall, this review views nanotechnology as an enabling technology to improve therapeutic effectiveness, minimize toxicity and open new avenues toward next-generation smart and personalized therapeutics for the treatment of PCM. Full article

A rapid, colorimetric sensor for histamine detection is presented using citrate-stabilized gold nanoparticles enhanced with Cu²⁺ coordination. The sensing mechanism involves dual recognition: protonated histamine first adsorbs electrostatically onto AuNP surfaces at pH 5.5, followed by Cu²⁺-mediated coordination between imidazole rings that induces interparticle coupling, resulting in a characteristic shift of the localized surface plasmon resonance from 520 to 620 nm. The optical response, measured as the absorbance ratio A₆₂₀/A₅₂₀, exhibits excellent linearity over the range of 1.25–10 μM with a detection limit of 0.95 μM and total assay time under 30 min. The dual-recognition mechanism provides high selectivity for histamine over structural analogs, including L-histidine, imidazole, and L-lysine. The metal ion-mediated colorimetric approach described here achieves sub-micromolar sensitivity in simple buffer solutions, which is comparable to the histamine level used in in vitro cell assays and food-related studies. Thus, the present system is best viewed as a mechanistic model that can inform the design of future biosensing and analytical methods, rather than as a fully optimized sensor for direct clinical measurements in complex biofluids. Full article