Search Results (1,786)

Cryptococcosis, caused by Cryptococcus neoformans, remains a major cause of mortality in immunocompromised patients, with treatment increasingly limited by resistance and toxicity associated with Amphotericin B (Amp B). In this study, methylglyoxal (MG) was evaluated as a virulence-targeted antifungal strategy, with emphasis on its liposomal delivery. MG exhibited superior antifungal activity as compared to Amp B, demonstrating lower MIC values and significantly enhanced inhibition of biofilm formation and laccase activity, key determinants of cryptococcal pathogenicity. Notably, MG showed potent intracellular antifungal activity within macrophages, where C. neoformans persists. Liposomal MG (Lip-MG) markedly reduced macrophage-associated fungal burden under the tested conditions, markedly outperforming both free MG and Amp B formulations. In a leukopenic mouse model of systemic infection, liposomal MG significantly improved survival (up to ~70%) and reduced pulmonary fungal burden as compared to Amp B, which showed limited therapeutic benefit. Importantly, MG-based formulations exhibited a favorable safety profile, with significantly lower nephrotoxicity than Amp B. Collectively, these findings demonstrate that Lip-MG acts through a dual virulence-targeted activity mechanism while effectively eliminating intracellular infection. This dual action, combined with improved safety, highlights MG-based nanotherapy as a promising and translational alternative for the treatment of drug-resistant cryptococcosis. Full article

Background/Objectives: This study aimed to develop a novel tumor-associated macrophage (TAM)-targeting nanoplatform to improve the solubility and bioavailability of camptothecin (CPT) and achieve active targeted drug delivery for enhanced anti-tumor immunotherapy. Methods: We constructed a sialic acid-disulfide bond-camptothecin (SA-SS-CPT) nanowire system. Sialic acid was used as a targeting ligand to specifically recognize the overexpressed Siglec-E receptor on TAMs. Upon cellular internalization, the disulfide bond was designed to respond to intracellular glutathione (GSH), enabling controlled drug release. Results: The SA-SS-CPT nanowires significantly improved CPT solubility and enabled targeted delivery to TAMs. Following GSH-responsive cleavage and CPT release, the nanowires induced DNA damage in TAMs, activating the cGAS-STING signaling pathway. This promoted TAM polarization toward the M1 phenotype, enhanced pro-inflammatory and anti-tumor immune responses, and inhibited tumor immune escape. Furthermore, SA-SS-CPT synergistically improved the efficacy of PD-L1 blockade immunotherapy, remodeling the tumor immune microenvironment. Conclusions: The SA-SS-CPT nanoplatform effectively targets TAMs, repolarizes them to an anti-tumor M1 phenotype, and activates the cGAS-STING pathway. It shows strong potential for overcoming tumor immune escape and synergizing with PD-L1 checkpoint blockade to achieve significant tumor clearance. Full article

Apitherapy is a complementary therapeutic approach based on the use of bee-derived products, particularly bee venom (BV), also known as apitoxin. Bee venom is a complex mixture of biologically active compounds, including peptides, enzymes, and biogenic amines, that exhibit diverse pharmacological activities. Major bioactive constituents such as melittin, apamin, adolapin, and phospholipase A2 have attracted increasing scientific interest due to their anti-inflammatory, antioxidant, antimicrobial, analgesic, and immunomodulatory properties. This review provides a comprehensive overview of the biological effects and therapeutic potential of bee venom in the management of chronic diseases, particularly diabetes, cancer, and neurological disorders. Evidence from experimental and clinical studies suggests that BV and its components can modulate multiple molecular pathways associated with oxidative stress, inflammation, apoptosis, and immune responses. These mechanisms contribute to potential benefits in glycemic control, tumor suppression, neuroprotection, and pain management. Additionally, bee venom has been investigated for its capacity to influence signaling pathways involved in cellular proliferation and survival, highlighting its potential as a complementary strategy in the treatment of complex diseases such as neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Despite these promising therapeutic effects, the clinical use of BV remains limited due to safety concerns, particularly the risk of allergic reactions, systemic toxicity, and anaphylaxis. Recent advances in drug delivery systems and nanotechnology may help improve the safety and efficacy of BV-based therapies by enabling targeted delivery and controlled dosing. Overall, bee venom represents a promising source of bioactive compounds with potential applications in translational and integrative medicine; however, further well-designed clinical trials and mechanistic studies are necessary to establish its safety, efficacy, and long-term therapeutic value. Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano–bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future. Full article

Depression is one of the most common mental disorders in modern society, and it has become a serious threat to human health. The limitations of existing antidepressant drugs have prompted people to turn to the multi-target, low-toxic side effects of natural products. This article reviews the conventional nutrients (omega-3 fatty acids, folic acid, and mineral elements) and functional active ingredients (flavonoids, polysaccharides, saponins, and terpenoids) in medicinal and food homologous substances (MFHs). They show antidepressant potential by regulating neurotransmitters, improving hypothalamic–pituitary–adrenal (HPA) axis function, promoting neuroplasticity, inhibiting neuroinflammation, regulating ferroptosis, and interfering with the gut–brain axis. In addition, this paper discusses the application prospects of modern technologies such as microbial fermentation and nano-delivery in improving the bioavailability of MFHs and product development. In summary, MFHs have potential application value in dietary intervention and adjuvant therapies for depression; in the future, randomized controlled clinical trials should be strengthened, and multi-omics technology should be combined to promote the development of precision products so as to provide a new perspective for the development of new antidepressant drugs. Full article

Currently, gold nanoparticles are increasingly used in targeted drug delivery nanostructures. However, their intrinsic catalytic activity is often overlooked when using them as a carrier. In this study, the interaction between the sotalol drug from the beta-blocker family and gold nanoparticles was investigated using capillary electrophoresis and high-performance liquid chromatography. Both methods showed that sotalol undergoes catalytic oxidation on the surface of citrate-stabilized gold nanoparticles into three products. Together with a cleavage of the isopropyl group from the nitrogen atom, the oxidation at the hydroxyl group occurs with the formation of a ketone. Analysis of electropherograms showed 100% conversion of sotalol after 48 h of incubation at a surface coverage of 1.2 × 10¹⁹ molecules per m². To examine the role of reactive oxygen species, the experiments were performed in oxygen-saturated and oxygen-deficient gold nanoparticle dispersions. The effects of radical scavenger additives and pH of nanoparticle dispersion were also assessed. The influence of surface ligands on sotalol conversion was studied using gold nanoparticles coated with thiols, surfactants, and polyelectrolytes. Based on comprehensive data, the mechanism of gold-nanoparticle-assisted multicenter oxidation of sotalol is proposed. Full article

Manganese-based nanomaterials have been novel multifunctional platforms in tumor immunotherapy because of their tunable multivalent states, biocompatibility, and multi-stimulus responsiveness. Current cancer treatments are insufficient and cause severe side effects; therefore, manganese-based nanomaterials are proposed in combination with immunotherapy to mitigate adverse effects. This review outlines the antitumor effects mediated by four key mechanisms: (1) activation of the cGAS-STING immune signaling pathway, (2) direct activation of immune cells, (3) induction of immunogenic cell death (ICD), and (4) modulation of the tumor microenvironment. These approaches are broadly categorized into two types: monotherapy and multimodal combination therapy. Monotherapy encompasses three specific modalities: (1) direct use as a Stimulator of Interferon Genes (STING) agonist, (2) vector-mediated targeted drug delivery, and (3) mediation of chemodynamic therapy to generate reactive oxygen species, thereby inducing ICD. Multimodal combination therapy involves synergistic integration with traditional or emerging treatment modalities, including chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy, and low-level light therapy, as well as multimodal combination treatment methods. It significantly enhances the antitumor efficacy of traditional therapies through immunostimulation, thus achieving synergistic breakthroughs in treatment efficiency and survival rate. Collectively, the multifunctional integration of manganese-based materials is a novel strategy for developing “self-adjuvant” immunotherapeutic platforms and investigating the clinical translation potential. Full article

Glaucoma is a collection of disorders that result in permanent vision loss and is characterized by a gradual decline in retinal ganglion cells. While it may not always be high, intraocular pressure (IOP) is the sole risk factor that can be modified according to extensive clinical research. Glaucoma remains the leading cause of irreversible blindness, yet early treatment lowering intraocular pressure is effective in slowing the rate of visual deterioration. Issues like poor absorption, low bioavailability, and short drug resistance time have thus made the management of glaucoma challenging when using conventional ophthalmic drugs. Thus, extensive research has been conducted to explore specific nanodrug delivery systems from various nanocarriers such as nanoparticles, micelles, liposomes and nanofibers, with a focus on systems that have achieved drug release for more than 12 h. These carriers have demonstrated substantial improvements in a lot of the evaluated aspects: enhancing ocular barrier-crossing capabilities, improving bioavailability, prolonging drug release, targeting active tissues of interest, and reducing IOP. This review covers recent developments in nanocarrier ocular delivery systems regarding the management of glaucoma. In this study, the advantages and disadvantages of each system were evaluated and their potential for advancing translation from research to clinic were assessed. Full article

Glioma, the most common and aggressive primary brain tumor, presents significant clinical management challenges due to difficulties in blood–brain barrier penetration, high tumor heterogeneity, and susceptibility to drug resistance and recurrence, leading to an extremely poor prognosis. Traditional Chinese Medicine (TCM), particularly its derived active ingredients and herbal formulations, with its advantages of multi-component, multi-target, and holistic regulation, demonstrates significant potential in the comprehensive treatment of this disease. This review systematically outlines the research progress in TCM for combating glioma. Regarding mechanisms of action, active TCM components not only directly inhibit tumors by inducing cell apoptosis but also exert synergistic therapeutic effects via multiple pathways. These include remodeling the immunosuppressive microenvironment, activating novel cell death programs such as ferroptosis and immunogenic cell death, intervening in tumor metabolic reprogramming, and reversing chemotherapy resistance. In terms of overcoming delivery barriers, drug delivery systems represented by nanocarriers, liposomes, and extracellular vesicles, combined with the penetration-enhancing effects of aromatic orifice-opening herbs (a class of TCM medicinals traditionally used to “open the orifices” and awaken the mind, now recognized to transiently enhance BBB permeability), have significantly improved the brain-targeting efficiency and bioavailability of TCM components. For clinical translation, a number of innovative drugs derived from TCM, such as elemene, cinobufagin, and ACT001, are currently under clinical investigation, with initial results showing efficacy in prolonging survival and improving quality of life. In the future, by integrating the analysis of multi-target synergistic mechanisms, promoting the clinical translation of intelligent drug delivery systems, and conducting high-quality clinical research on integrated Chinese and Western medicine, TCM is expected to provide a new generation of integrated treatment strategies for glioma that combines holistic and precision medicine. Full article

Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD. Full article

Traditional pharmacotherapy is often constrained by suboptimal bioavailability and systemic toxicity. Biomolecularly inspired nano-drug delivery systems (nano-DDS) have emerged as precise platforms to overcome these barriers by orchestrating molecular interactions at the bio-nano interface. This review systematically evaluates the molecular recognition mechanisms and biochemical principles governing nano-DDS performance. We systematically evaluate how passive targeting relies on the EPR effect—dictated by the nanocarrier’s physicochemical properties—and how active targeting exploits ligand-receptor affinity to enhance cellular uptake. Special emphasis is placed on bioresponsive strategies that utilize pathological cues—such as pH gradients, redox potential, and enzymatic activity—for intelligent, on-demand drug release. Furthermore, we discuss structure-function relationships in lipid, polymeric, and biologically derived systems, highlighting their roles in modulating therapeutic signaling in oncology and inflammatory diseases. Finally, translational hurdles and emerging AI-driven molecular design strategies are critically examined. Full article

Bletilla striata polysaccharide (BSP), a bioactive glucomannan derived from the traditional Chinese medicinal herb Bletilla striata, has garnered increasing attention in both the biomedical and food sectors due to its unique physicochemical properties and diverse biological activities. While existing reviews have partially covered BSP’s structural features or single-field applications, a systematic review integrating its structure–activity relationship, full-spectrum chemical modification strategies, and parallel advances in the dual core fields of biomedicine and the food industry remains lacking. This review systematically consolidates recent advances in BSP research, focusing on three interconnected aspects: (1) the structure–activity relationships of BSP, highlighting how molecular weight (10⁴–10⁵ Da), monosaccharide composition (mainly glucose and mannose with variable ratios), glycosidic linkages, and higher-order self-assembled structures (e.g., triple-helix conformation) dictate its functionality in biological systems and food matrices; (2) chemical modification strategies—including carboxymethylation, graft copolymerization, cross-linking, polysaccharide–trace element complexation, phosphorylation, acetylation, and cholesterylation—that overcome intrinsic limitations of native BSP to enhance solubility, targeting, bioactivity, and food-related functional properties; and (3) the expanding applications of BSP and its derivatives in biomedicine (hemostatic materials, tissue engineering scaffolds, drug delivery systems, immunomodulation, and antitumor effects) and in the food industry (as natural stabilizers, emulsifiers, functional additives, and bio-based packaging components). Compared with previously published reviews, this work establishes a complete closed-loop logical system from structural characterization to rational modification and cross-field application and provides the most up-to-date systematic summary of BSP research. Key challenges—such as an incomplete understanding of structure-function correlations, insufficient pharmacokinetic data, and a lack of standardized quality control—are discussed, and future research directions are proposed. This review aims to provide a systematic theoretical basis for advancing BSP as a versatile multifunctional material for applications in functional foods, nutraceuticals, and biomedical fields. Full article

Rationale: Oral squamous cell carcinoma (OSCC) carries a poor prognosis despite advances in multimodal therapy. Nanomedicine represents a compelling strategy to enhance targeted drug delivery and improve therapeutic outcomes. Here, we investigated sEV-mediated delivery of curcumin as a novel therapeutic approach for OSCC. Methods: Small extracellular vesicles (sEVs) were isolated from Jurkat cells by size-exclusion chromatography and loaded with curcumin via sonication to generate JCsEV. Functional effects were assessed in vitro using wound healing, transwell invasion, and metabolic activity assays across multiple cancer cell lines. Therapeutic efficacy in vivo was evaluated in the 4-nitroquinoline 1-oxide (4-NQO) immunocompetent murine model of oral carcinogenesis. Female C57BL/6J mice received intraperitoneal treatment for four weeks with PBS, free curcumin, unloaded JsEV, or JCsEV. Tumor number, tumor burden, and body weight changes were assessed at the experimental endpoint. Results: In vitro, JCsEV significantly inhibited tumor cell migration, invasion, and metabolic activity compared with controls (p < 0.05). In vivo, treatment with JCsEV significantly reduced tumor number and tumor burden in the 4-NQO model (p < 0.01). In addition, body weight loss was reduced in JCsEV-treated mice compared with controls. Conclusion: sEV-mediated delivery of curcumin effectively suppresses tumor progression in experimental OSCC. These findings establish proof-of-concept for sEV-based nanomedicine as a therapeutic strategy for OSCC and provide a compelling rationale for further translational investigation of sEVs as drug delivery platforms. Full article

Halloysite nanotubes (HNTs), composed of an aluminosilicate framework, are naturally abundant, biocompatible, and sustainable clay minerals with a tubular morphology and tunable surface chemistry, making them attractive platforms for targeted, multifunctional drug delivery systems. In this study, a zinc ferrite integrated halloysite nanocomposite (ZnFe₂O₄/HNT) was developed via a one-pot synthesis approach for sustained release of cisplatin (Cp), aiming to reduce systemic toxicity and enhance cell-specific activity. The nanocomposites were further functionalized by integrating Cp (Cp: ZnFe₂O₄/HNT ratio 0.05) and folic acid (ZnFe₂O₄/HNT/Cp: FA ratio 0.05), followed by PEGylation (0.17 µL/mg of ZnFe₂O₄/HNT/Cp/FA/PEG). The structural and surface characteristics, phase, interfacial interactions (FA and Cp), and colloidal stability of nanoformulations were systematically investigated using powder X-ray diffraction analysis (XRD), Fourier transformed infrared (FT-IR) spectroscopy, zeta potential analysis, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), and diffuse reflectance UV–visible (DRS-UV-Vis) spectroscopy. The results confirmed that ZnFe₂O₄ integration preserved the clay’s tubular framework while inducing nanocrystallization of both ferrite and cisplatin, indicating molecular dispersion within the clay matrix. Functionalization with FA (ZnFe₂O₄/HNT/Cp/FA) promoted amide bond linkage, modulated Cp-FA interactions, and significantly enhanced cumulative Cp release compared to the non-functionalized system ZnFe₂O₄/HNT/Cp (10.3% at 72 h vs. 34.4% at 72 h) under tumor acidic conditions (pH 6.6). PEGylation maintained the controlled release profile while improving dispersion stability. In vitro cytotoxicity studies revealed that FA-conjugated nanocomposites exhibited enhanced, time-dependent anticancer activity against HeLa cervical cancer cells, with reduced toxicity toward normal fibroblasts, indicating preferential cellular uptake via folate receptor-mediated mechanism. Overall, this work demonstrates that FA-functionalized ZnFe₂O₄/HNT nanocomposite provides an effective clay-based platform for modulating Cp release and enhancing folate receptor protein-mediated targeted therapy for cervical cancer. Full article