Search Results (924)

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a leading cause of death from a single infectious agent worldwide. Conventional antibiotic therapies face significant limitations, including multidrug resistance, poor treatment adherence, limited penetration into granulomas, and systemic toxicity. Recent advances in nanomedicine have paved the way for nanotheranostic approaches that integrate therapeutic, diagnostic, and preventive functions into a single platform. Nanotheranostic systems enable targeted drug delivery to infected macrophages and granulomatous lesions, real-time imaging for disease monitoring, and controlled, stimuli-responsive release of antitubercular agents. These platforms can be engineered to modulate host immune responses through host-directed therapies (HDTs), including the induction of autophagy, regulation of apoptosis, and macrophage polarization toward the bactericidal M1 phenotype. Additionally, nanocarriers can co-deliver antibiotics, immunomodulators, or photosensitizers to enhance intracellular bacterial clearance while minimizing off-target toxicity. The review also discusses the potential of nanotechnology to improve TB prevention by enhancing vaccine efficacy, stability, and targeted delivery of immunogens such as BCG and novel subunit vaccines. Key nanoplatforms, including polymeric, lipid-based, metallic, and hybrid nanoparticles, are highlighted, along with design principles for optimizing biocompatibility, multifunctionality, and clinical translatability. Collectively, nanotheranostic strategies represent a transformative approach to TB management, bridging diagnosis, therapy, and prevention in a single, adaptable platform to address the unmet needs of this global health challenge. Full article

The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article

Hepatocellular carcinoma (HCC) represents the predominant type of primary liver cancer and remains a major global health concern. Current therapeutic strategies—such as surgical resection, radiation, and chemotherapy—provide clinical benefits but are frequently accompanied by considerable adverse effects. Consequently, identifying alternative treatment modalities and developing strategies that allow the use of lower drug doses without compromising therapeutic outcomes are essential goals in HCC management. Among emerging nanoscale platforms, metal–organic frameworks (MOFs) have attracted exceptional interest as promising candidates for targeted drug delivery in cancer therapy. Their inherent characteristics, including highly ordered porosity, large surface area, tunable cavities, adjustable chemical functionality, and remarkable drug-loading capacity, set them apart from conventional porous nanomaterials. Owing to their hierarchical architecture, MOFs are especially suitable for multimodal and synergistic anti-cancer treatments. MOF-based systems have demonstrated the ability to reinforce the performance of several therapeutic modalities, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT), while also serving as efficient carriers for targeted drug release. Their structural versatility further enables improved drug stability, enhanced solubility, and controlled-release behavior. This review provides an overview of recent progress in MOF-enabled therapeutic strategies and discusses their potential applications in the treatment of HCC. Full article

We report the synthesis and biological characterization of N-heterocyclic carbene (NHC) complexes with gold(I), silver(I), copper(I), and palladium(II) metal centers, and 3-(2,6-diisopropyl-phenyl) imidazolinium- and imidazolium-based ligands, including their biscarbene complexes, along with metal complexes of 4-(S)-tert-butyl-imidazolinium-derived carbenes carrying various substituents in position 1. Compared to the imidazolium complexes, the corresponding imidazolinium complexes displayed superior cytotoxicity against the Mes-Sa uterine sarcoma cell line, while the biscarbene complexes exhibited greatly enhanced cytotoxicity with nanomolar activity. The ABCB1-overexpressing multidrug-resistant sublines of Mes-Sa demonstrated only marginal resistance to monocarbene imidazolinium complexes lacking a 4-(S)-tert-butyl group, whereas significant resistance was observed for all other complexes, with its extent further influenced by the nature of the metal center. Probing a subset of the complexes confirmed their strong cytotoxicity against the CST murine breast cancer cell line and its cisplatin-resistant variant, with little or no cross-resistance observed. Within a defined subset, compounds triggered apoptosis, and intracellular ROS production was consistently induced by the copper complexes. Collectively, these results indicate that imidazolinium-based metal NHCs are promising anticancer drug candidates, with copper and silver centers standing out for their potent cytotoxicity and evasion of both ABCB1-mediated and cisplatin resistance. Full article

Significant efforts have been devoted to discovering novel metal-based complexes with better cytotoxicity and specificity to tumor cells. Within the range of complexes studied for cytotoxic activity, Ru complexes have gained significant attention as one of the most promising classes of compounds offering advantages such as good scaffolds for the construction of new bioactive molecules with a variety of ligands. Ruthenium-based compounds demonstrate efficient penetration into cancer cells and show affinity for DNA binding with antitumor mechanisms, other than those of cisplatin. They were identified as perfect chemotherapeutics for cancer treatment due to their good tolerance by normal cells, negligible toxic effects and stronger activity towards Pt-drug-resistant tumor cell lines. Ru-based complexes may interact with multiple targets and show selective accumulation in cancer cells, which enhances their therapeutic potential. In recent years, the design of polynuclear complexes has aroused considerable interest in drug discovery research. The strategy to incorporate two or more metal centers into one precise molecular structure may result in better cytotoxic activity compared to the mononuclear precursors. That is why ruthenium-based multinuclear anticancer organometallic and complex compounds have attracted lots of attention. The objective of the current review is to highlight the key results obtained in research on ruthenium complexes, presenting the up-to-date advances of multinuclear homometallic ruthenium complexes as promising anticancer candidates. The reported outcomes shed new light on the fundamental biological interactions and antineoplastic modes of action of ruthenium-based complexes and organometallic compounds as well as significant information for the prediction of novel anticancer drugs. Full article

Background: Cancer therapeutics development has been a challenge in medical and scientific areas due to their toxicity, limited biocompatibility, and unfortunate side effects. However, despite advances in early detection and the study of novel treatments, the mortality rate for breast cancer remains high, making it a significant global health concern. Objectives: In this study, poly(methyl methacrylate) (PMMA) nanoparticles functionalized with acrylic acid (AA), fumaramide (FA), and curcumin (CUR) as chelating and inhibitor agents were synthesized by emulsion polymerization techniques. Methods and Results: Comprehensive physiochemical characterization studies based on gravimetry, dynamic light scattering (DLS), electrophoresis, Fourier transform infrared (FT-IR), ultraviolet–visible (UV–Vis) and photoluminescence (PL) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) revealed a pH dependence of nanoparticles that exhibit structural changes upon interaction with calcium (Ca²⁺) and magnesium (Mg²⁺) ions. Calorimetric thermodynamic properties measured by isothermal titration calorimetry (ITC) confirmed chelating coordination and positive cooperativity between the nanoparticles and metal ions. In vitro studies showed the low cytotoxicity of nanoparticles by fibroblast proliferation, and their chelation process was observed by fluorescence microscopy, with the loss of interaction between cells. Conclusions: These results suggest that the functionalized nanoparticles have potential in drug delivery systems (DDS) for targeted breast cancer therapies, providing a promising polymer material for more efficient and less toxic treatments. Full article

Background: Mobile antimicrobial resistance genes (ARGs) on plasmids or other elements enable Salmonella Typhimurium to spread resistance across hosts and environments. The emergence of multi-drug resistance (MDR) Salmonella Typhimurium has raised global concern, yet little is reported about these mobile elements from the Thailand pork supply chain, where this risk of transfer to humans remains largely uncharacterized. Methods: Between March 2023 and February 2024, 25 S. Typhimurium isolates were collected from pig carcasses in slaughterhouses and pork swabs from retail markets in northeastern Thailand. Nine representative isolates, sampled across three seasons, were subjected to Illumina whole-genome sequencing. Assemblies were analyzed for sequence types, phylogenetic relationships, antimicrobial resistance (AMR) determinants, plasmid replicons and mobilization features, functional annotation based on COG (Clusters of Orthologous Groups of proteins) classification, and comparative genomics against a reference strain. Results: Genome assemblies ranged from 4.76 to 5.00 Mb with consistent GC (guanine-cytosine) content (52.0–52.2%). Phylogenetic analysis revealed three sequence types: ST34 (77.8%), ST19, and ST1543. ST34 isolates displayed the broadest AMR gene repertoires, carrying tetracycline (tetA/tetB), sulfonamide (sul1/sul2/sul3), aminoglycoside (aadA, aph(6)-Id, aph(3″)-Ib), phenicol (floR, catA1), and β-lactam (bla_TEM-1B) genes, whereas non-ST34 isolates harbored fewer determinants. ARGs frequently co-localized with IncQ1 and Col-type plasmid replicons, MOB_H/MobA relaxases (enzymes that initiate plasmid transfer), and conjugation modules (type IV secretion and coupling proteins), often alongside virulence loci and metal resistance operons. Functional annotation showed highly conserved metabolic and housekeeping functions, while comparative genomics confirmed >90% core genome conservation, with variability concentrated in genomic islands encoding hypothetical proteins. These genomic patterns were inferred from a limited WGS dataset (nine isolates) and should therefore be considered exploratory and require confirmation in larger collections. Conclusions: Multi-drug resistant ST34 Salmonella Typhimurium predominated in the northeastern Thailand pork supply chain, with diverse resistance genes carried on IncQ1/Col-type plasmids linked to MOB_H relaxases and conjugation modules. The stability of these mobilizable elements underscores their role in sustaining MDR traits and highlights the risk of foodborne AMR transmission, reinforcing the need for continuous genomic surveillance under a One Health framework. Full article

Sodium alginate, a natural anionic polysaccharide, exhibits broad potential applications in food, biomedicine, and environmental engineering due to its favorable biocompatibility, degradability, and functional tunability. This review systematically summarizes its chemical structure, physicochemical characteristics, sources, and extraction methods. It also focused on modification strategies, including chemical approaches (e.g., esterification, oxidation, sulfation, graft copolymerization), physical methods (composite modification, irradiation cross-linking, ultrasound treatment), and biological (e.g., enzyme regulation), and elucidated their underlying mechanisms. In the context of food science, special emphasis is placed on food-compatible chemistries and mild modification routes (such as phenolic crosslinking, enzyme-assisted coupling, and other green reactions) that enable the development of edible films, coatings, and functional carriers, while distinguishing these from non-food-oriented chemical strategies. The review further highlights novel applications of modified sodium alginate in areas including food packaging, functional delivery systems, drug release, tissue engineering, and environmental remediation (heavy metal and dye removal). Overall, this work provides a comprehensive perspective linking modification pathways to food-relevant applications and clarifies how chemical tailoring of alginate contributes to the design of safe, sustainable, and high-performance bio-based materials. Full article

Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation—key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy. Full article

This review paper presents a comprehensive literature analysis that elucidates the global engagement of research teams in addressing the important problem of finding effective oncology drugs based on the following platinum group metal ions: ruthenium, rhodium and iridium. The necessity to search for new drugs can be attributed, in part, to the predominance of platinum-based chemotherapeutics in clinical practice. However, these drugs face limitations in their clinical application due to their inherent toxicity and the development of resistance by cancer cells. A distinctive attribute of these metal compounds is the formation of diamagnetic stable complexes on +II (Ru) and +III (Rh, Ir) oxidation degrees with a d⁶ electron configuration, a coordination number of six and an octahedral or pseudo-octahedral structure. In this paper we have systematised the findings presented in the literature by classifying the most significant categories of ruthenium, rhodium and iridium compounds, namely piano-stool-type arenes, polypyridine and cyclometalated complexes, dimers and multinuclear complexes. Additionally, the most crucial research challenges connected with metal complexes that have been addressed by scientists have been presented: (i) the application of prodrugs in cancer therapy; (ii) the deployment of complexes as sensitizers in PDT and PACT; (iii) the exploration of complexes as inhibitors of enzymes and biocatalysts; and (iv) the investigation of multiple-target complexes. Furthermore, the objective was to emphasise the accomplishments in this domain in recent years by identifying compounds that have entered the clinical trial phase. Full article

The convergence of nanotechnology and bioaerogels has paved the way for the development of multimodal nanostructured bioaerogels with remarkable potential in smart drug delivery systems. These advanced biomaterials integrate multiple functionalities, including sensing, targeting, and therapeutic actions, to enhance drug efficacy, minimize systemic side effects, and enable real-time monitoring of therapeutic responses. This review provides a comprehensive analysis of the structural design, physicochemical properties, and fabrication strategies of multimodal bioaerogels. It further explores their role in responsive drug delivery, emphasizing stimuli-responsive mechanisms such as pH, temperature, and enzymatic triggers. The incorporation of nanomaterials, including metallic nanoparticles, carbon-based nanostructures, and polymeric nanocarriers, has endowed bioaerogels with tunable porosity, controlled drug release, and bioactive functionalities. Additionally, their application in precision medicine, particularly for cancer therapy, antimicrobial treatments, and tissue engineering, is critically examined. Challenges related to scalability, biocompatibility, and regulatory compliance are also discussed, alongside future perspectives on advancing these bioaerogels toward clinical translation. By integrating interdisciplinary insights, this review underscores the transformative potential of multimodal nanostructured bioaerogels in the next generation of intelligent drug delivery systems. Full article

The escalating threat of antibiotic resistance has prompted the search for alternative antibacterial therapies. Antibacterial photodynamic therapy (aPDT), which utilizes light-activated photosensitizers to generate reactive oxygen species (ROS), offers a promising, non-invasive approach. The aim of this review is to analyze recent advances in nanoparticle-mediated aPDT and synthesize crucial design principles necessary to overcome the current translational barriers, thereby establishing a roadmap for future clinically applicable antimicrobial treatments. Emerging nanoparticle platforms, including upconverting nanoparticles (UCNPs), carbon dots (CDs), mesoporous silica nanoparticles (MSNs), liposomes, and metal–organic frameworks (MOFs), have demonstrated improved photosensitizer delivery, enhanced ROS generation, biofilm disruption, and targeted bacterial eradication. Synergistic effects are observed when aPDT is integrated with photothermal, chemodynamic, or immunotherapeutic approaches. The review further examines the mechanisms of action, biocompatibility, and antibacterial performance of these nanoparticle systems, particularly against drug-resistant strains and in challenging environments such as chronic wounds. Overall, nanomaterial-mediated aPDT presents a highly promising and versatile solution to antimicrobial resistance. Future perspectives include the integration of artificial intelligence to personalize aPDT by predicting optimal light dosage and nanoplatform design based on patient-specific data, rigorous clinical validation through trials, and the development of safer, more efficient nanoparticle platforms. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is among the most aggressive subtypes, lacking estrogen, progesterone, and HER2 receptors, which limits the efficacy of targeted therapies. Standard treatments often fail due to rapid drug resistance and poor long-term outcomes. Repurposing approved drugs with anticancer potential offers a promising alternative. Disulfiram (DSF), an FDA-approved alcohol-aversion drug, forms a copper complex [Cu(DDC)₂] with potent anticancer activity, but its clinical translation is hindered by poor solubility, limited stability, and inefficient delivery. Methods: Here, we present an amphiphilic dendrimer-stabilized [Cu(DDC)₂] nanoparticle (NP) platform synthesized via the stabilized metal ion ligand complex (SMILE) method. Results: The optimized nanocarrier achieved high encapsulation efficiency, enhanced serum stability, and potent cytotoxicity against TNBC cells. It induced immunogenic cell death (ICD) characterized by calreticulin exposure and ATP release, while modulating the tumor microenvironment by downregulating MMP-3, MMP-9, VEGF, and vimentin, and restoring epithelial markers. In a 4T1 TNBC mouse model, systemic [Cu(DDC)₂] NP treatment significantly inhibited tumor growth without combinational chemo- or radiotherapy. Conclusions: This DSF-based metal–organic NP integrates drug repurposing, immune activation, and tumor microenvironment remodeling into a single platform, offering strong translational potential for treating aggressive breast cancers. Full article

Nanoparticles (NPs) have significantly changed the field of drug delivery, offering control over pharmacokinetics, biodistribution, and targeted therapy. Among these, ultrasmall nanoparticles (USNPs) with sizes of approximately 5–15 nm have garnered significant interest due to their unique physicochemical properties, including enhanced cellular uptake, deeper tissue penetration, and prolonged systemic circulation. This review explores the fundamental principles governing sub-15 nm nanoparticles, their classification, and their distinctive advantages in pharmaceutical applications. Various types of nanoparticles, including polymeric, lipid-based, metallic, and carbon-based nanosystems, are examined in the context of drug delivery in cancer therapy. We detail how sub-15 nm polymeric nanoparticles (PNPs) are emerging as transformative drug delivery platforms for cancer therapy. The impact of nanoparticle size, surface modifications, and biocompatibility on therapeutic performance is critically analyzed. Furthermore, we discuss emerging applications of these ultrasmall nanoparticles in cancer therapy, neurological disorders, vaccine delivery, and imaging. Despite their promise, key challenges such as stability, aggregation, toxicity, and regulatory concerns remain significant hurdles for clinical translation. This review provides insights into the potential of 5–15 nm nanoparticles to reshape modern drug delivery and highlights future directions for research and development in this rapidly evolving field. Full article

Gold (Au) and silver (Ag) nanoparticles (NPs) are used for drug transport and plant protection due to their insoluble nature and unique properties. To produce health-friendly NPs, toxic solvents should be replaced with plant-based synthesis. Plants, such as alfalfa (Medicago sativa L.), release biomolecules that reduce metal ions and form nanoclusters without free radicals, showing anti-inflammatory and antioxidant properties. In this study, callus cultures of two M. sativa genotypes, ‘Kometa’ and ‘La Bella Campagnola’, were exposed to two precursors (AgNO₃ and HAuCl₄) for 24 and 48 h to assess the feasibility of biological NP synthesis. Spectrophotometry showed significant (p ≤ 0.05) changes in light absorbance compared with the control. Dynamic light scattering and zeta potential measurements indicated a change in the composition of the liquid compared with the control. To improve image quality and obtain more accurate data, transmission electron microscopy (TEM) analysis was repeated, confirming the presence of quasi-spherical nanoparticles with diameters in the range of 5–25 nm for both AuNPs and AgNPs in the callus culture extracts of both genotypes. Nanoparticle Tracking Analysis demonstrated that the AgNPs and AuNPs from both genotypes displayed polydisperse size distributions, with a mean particle size ranging from 220 to 243 nm. Elemental analysis provided clear evidence that Ag and Au were present only in treated samples, confirming effective NP biosynthesis and excluding contamination. X-ray diffraction (XRD) analysis was performed to characterise the crystalline structure; however, due to the very small particle size (5–25 nm), no clear diffraction patterns could be obtained, as nanocrystals below ~20–30 nm typically produce signals below the detection limit of standard XRD instrumentation. The novelty of this research is the cost-effective, rapid biosynthesis of quasi-spherical AuNPs and AgNPs with diverse sizes and enhanced properties, making them more eco-friendly, less toxic, and suitable for antibacterial and anticancer studies. Full article