Search Results (2,455)

Background: Metal-based anticancer drugs, particularly platinum and gold complexes, play a central role in chemotherapy but are often limited by systemic toxicity, resistance, and suboptimal selectivity. Peptide conjugation has emerged as a versatile strategy to modulate the pharmacokinetic and biological properties of metal complexes, enabling targeted delivery, improved uptake, and controlled activation. This review aims to critically analyze platinum- and gold-peptide bioconjugates in cancer therapy, focusing on directly reactive metal complexes and redox-activated prodrug systems. Methods: Relevant literature from the past two decades was surveyed across major scientific databases, focusing on the design, conjugation strategies, biological activity, and mechanisms of action of Pt- and Au-peptide bioconjugates. Results: Reviewed studies reveal distinct behavior for platinum- and gold-based systems. Pt(II)-peptide conjugates primarily retain DNA-reactive interaction, with peptides mainly enhancing cellular uptake, selective targeting and solubility, although improved cytotoxicity is not consistently achieved. In contrast, Pt(IV)-peptide conjugates function as prodrugs, where axial peptide functionalization allows greater structural versatility and sometimes improved selectivity, with therapeutic efficacy strongly depending on intracellular reduction kinetics. Au(I)-peptide conjugates act as directly reactive species targeting thiol- and selenol-containing proteins, whereas Au(III) bioconjugates often behave as redox-activated prodrugs, with peptide conjugation influencing stability and cellular fate. Conclusions: Overall, peptide conjugation represents a powerful but non-trivial approach for optimizing metal-based anticancer agents. The success of metal-peptide bioconjugates critically depends on balancing peptide-mediated delivery with the intrinsic reactivity and activation pathways of the metal center. A function-guided design of bioconjugates is essential to achieve genuine selectivity and therapeutic benefit. Full article

Oral mucosal repair is a redox-regulated process that may be impaired by diabetes, chronic inflammation, infection, and chemotherapy- or radiotherapy-induced oral mucositis. Reactive oxygen species (ROS) support host defense, epithelial migration, angiogenesis, extracellular matrix remodeling, and adaptive repair when their production is transient and compartmentalized. In contrast, persistent ROS promote lipid, protein, and DNA oxidation, mitochondrial dysfunction, and extracellular matrix damage. Photobiomodulation (PBM) is increasingly used to support oral tissue repair, but its effects should be interpreted as dose- and context-dependent redox modulation rather than as simple antioxidant activity. This narrative review synthesizes oxidative stress biomarkers and redox-sensitive pathways relevant to oral mucosal repair and PBM, including oxidant–antioxidant balance, lipid and protein oxidation, oxidative DNA damage, antioxidant defense, thiol/disulfide homeostasis, mitochondrial and NADPH oxidase-derived ROS, Nrf2/HO-1, NF-κB, HIF-1α/VEGF, MAPK/ERK, PI3K/Akt, and MMP/TIMP signaling. The review emphasizes the distinction between transient mitochondrial ROS/nitric oxide signaling and sustained NADPH oxidase-driven oxi-inflammatory stress. It proposes a practical redox-guided framework for biomarker selection, PBM response interpretation, and future study design, while noting that this framework remains conceptual and is not yet a validated clinical decision algorithm. Full article

Gold nanoparticles (AuNPs) have emerged as versatile antiviral nanoplatforms because their size, morphology, plasmonic properties, and surface chemistry can be precisely engineered. In this review, we summarize the core design principles of antiviral AuNPs from a structure–function–mechanism perspective. We first outline representative synthetic and interface-programming routes for AuNP preparation, including citrate reduction, Brust–Schiffrin synthesis, seed-mediated growth, green synthesis, direct thiol-conjugation, and mixed-ligand shell strategies, emphasizing how these approaches define particle size, morphology, surface accessibility, interfacial composition, and downstream biofunctionalization potential. We then discuss major surface engineering strategies, including polyethylene glycol, nucleic acids, antibodies and nanobodies, peptides, glycans, antiviral drugs, and biomimetic coatings, with particular attention to how ligand density, orientation, flexibility, and interfacial stability determine biological performance. Next, we examine how functionalized AuNPs inhibit different stages of the viral life cycle, including viral attachment and entry, intracellular replication, assembly and egress, photothermal inactivation, and immune modulation or vaccine delivery. Finally, we highlight current challenges, including incomplete structure–activity relationships, dynamic nano–bio interactions under physiological conditions, limited standardization across studies, and translational barriers related to safety, reproducibility, and scale-up. This review provides a conceptual framework for the rational development of next-generation AuNP-based antiviral nanotherapeutics. Full article

Copper ions (Cu²⁺) and intracellular biothiols are tightly coupled in cellular redox regulation, where copper–thiol coordination governs oxidative stress and metal homeostasis. However, analytical platforms capable of sequentially monitoring Cu²⁺ and biothiols within a single molecular system remain scarce. Herein, we report a coumarin-based fluorescent probe XDP that enables sequential ON–OFF–ON sensing of Cu²⁺ and biothiols through a coordination–competition mechanism. The imine (C=N) site of XDP selectively coordinates Cu²⁺, leading to fluorescence quenching arising from coordination-induced electronic perturbation and enhanced nonradiative decay. The probe exhibits a linear response toward Cu²⁺ over 1–80 μM with a detection limit of 0.108 μM. Subsequent competitive binding of biothiols (GSH, Cys, and Hcy) releases Cu²⁺ from the complex, thereby restoring fluorescence and enabling detection within 1–30 μM with submicromolar sensitivity. XDP also displays a large Stokes shift (135 nm), which minimizes spectral overlap and improves signal reliability. Notably, Cu²⁺ binding triggers a distinct color change that supports naked-eye detection and smartphone-based RGB quantification. The probe further enables visualization of Cu²⁺ and thiol-triggered signal recovery in living cells and zebrafish. This work establishes a versatile analytical platform for probing copper–thiol interactions in environmental and biological systems. Full article

To understand glycan–protein interactions at biological interfaces, designing surfaces modified with structurally controlled glycans is highly important. In particular, naturally occurring glycosaminoglycans (GAGs) possess periodic sugar arrangements that play important roles in protein recognition, highlighting the need for the development of periodic glycopolymer model systems that can serve as GAG mimics for quantitative interaction analysis. In this study, sequence-controlled periodic glycopolymers were synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization and immobilized onto gold surfaces to construct glycan-modified interfaces. The synthesized material was a terminally functionalized periodic glycopolymer with the most basic structure, consisting of alternating maltose-containing vinyl ether (MalVE) units and ethyl maleimide (EtMI) units, with a trithiocarbonate group at the ω-terminal. This trithiocarbonate group was converted to a thiol group for immobilization through Au–S bond formation. Structural characterization by ¹H NMR spectroscopy, size exclusion chromatography (SEC), MALDI-TOF mass spectrometry, and UV–vis spectroscopy confirmed the structure as designed. Quartz crystal microbalance (QCM) measurements verified the stable immobilization of thiol-terminated periodic glycopolymers on the gold surface, and allowed for estimation of graft density and quantitative analysis of glycan-protein interactions at the modified interface. The periodic glycopolymer-modified surfaces exhibited selective binding behavior toward concanavalin A (ConA) compared to bovine serum albumin (BSA), with apparent binding constants on the order of 10⁶–10⁷ L mol⁻¹. This enhanced binding behavior indicated that specific and multivalent interactions with proteins also occurred at periodic pendant maltose residues along the main chain. These results demonstrate that the gold surface modified with end-functional periodic glycopolymers synthesized by RAFT polymerization provides a versatile platform for quantitative analysis of glycan-protein interactions and suggests potential applications for periodic glycopolymers as functional materials. Full article

Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm² of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm²), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration. Full article

Atherosclerosis is a progressive vascular disease characterized by lipid-rich plaque accumulation, oxidative stress, and chronic inflammation, contributing to coronary heart disease, stroke, and peripheral arterial disease. This study investigated the impact of inflammation, vascular calcification, and statin therapy on redox balance in blood and carotid artery plaques, aiming to identify potential biomarkers for disease assessment. Thirty-two patients undergoing carotid endarterectomy provided 34 plaque samples. Enzyme activities in plaque/erythrocytes and –SH group concentration in plasma/plaque were measured. Pathological analysis was performed to determine inflammation/calcification grade, the presence of mast cells and plaque composition. The results showed that mast cells were associated with reduced non-protein –SH groups, indicating selective thiol consumption and serving as a qualitative marker of oxidative burden. Reduced catalase activity in erythrocytes was associated with advanced calcification, pointing to long-standing systemic oxidative stress. Statin therapy enhanced systemic superoxide-dismutase 1 activity, increased –SH groups, and modulated plaque-specific glutathione reductase activity, attenuating sex-related differences in redox regulation. These findings highlight the complex interplay between systemic and local oxidative processes in atherosclerosis through alterations in redox-related biomarkers such as plasma –SH group concentrations and catalase activity. Full article

Reactivity of non-aromatic 2,5-dichloro-2H-pyrroles toward S-nucleophiles was investigated. It was found that these non-aromatic derivatives exhibit both oxidative and electrophilic properties. Their reaction with thiols and xanthates proceeds as redox process to form disulfides and 5-chlorinated pyrroles as a result of 2,5-dichloro-2H-pyrroles reduction. However, the reaction with ammonium thiocyanate afforded the corresponding 5-thiocyanated 1H-pyrroles. Based on these findings, a novel one-pot method for the thiocyanation of 2,3,4-trisubstituted pyrroles was developed. The protocol involves the in situ generation of highly reactive 2,5-dichloro-2H-pyrroles via dearomative chlorination of the corresponding pyrroles using trichloroisocyanuric acid (TCCA). Subsequent addition of ammonium thiocyanate leads to regioselective incorporation of a thiocyanate group at the C5 position and rearomatization of the pyrrole core. A broad scope of pyrrole-5-thiocyanates was obtained in yields up to 82%. Furthermore, these derivatives were efficiently transformed into 5-trifluoromethylthiolated pyrroles using Ruppert’s reagent in up to 94% yield. This reaction sequence provides a cost-effective way to obtain 5-trifluoromethylthiolated pyrroles, avoiding the need for high-cost electrophilic reagents. The synthetic utility of these novel sulfur-containing pyrrole derivatives was also demonstrated. Full article

Selenium has played a fundamental role in the evolution of aerobic life, thanks to its unique redox properties and its incorporation into antioxidant selenoproteins such as glutathione peroxidases (GPx). This evolutionary perspective has inspired decades of research aimed at developing small organoselenium compounds as GPx-like antioxidant drugs. However, despite extensive in vitro evidence and numerous publications, no organoselenium antioxidant has been commercialized, and even Ebselen, the most extensively studied selenium-based drug candidate, has repeatedly failed in multiple clinical trials. In this opinion article, we posit the hypothesis that a conceptual bias may underlie a significant proportion of the research conducted to date in this field. The antioxidant activity of GPx is contingent on a highly regulated enzymatic environment that is extremely difficult to reproduce with small synthetic molecules. Consequently, many compounds described as GPx mimetics may behave less like true antioxidants and more like redox-active electrophiles capable of disrupting complex thiol-dependent equilibria. It is recommended that future research should adopt a more holistic approach to the study of selenium pharmacology, moving beyond a reductionist interpretation of GPx-like activity. Instead, the focus should be on the complex network of cellular redox processes and selective redox targeting. It is only through a more profound mechanistic comprehension of selenium chemistry within biological systems that it will be feasible to ascertain whether organoselenium compounds can genuinely establish a presence within the domain of medicinal chemistry, extending beyond their persistent yet predominantly laboratory-restricted achievements. In a similar vein, undertaking a thorough examination of the mechanisms may facilitate a more profound comprehension of the fate of organoselenium compounds in their intricate interaction with biological targets. This, in turn, may enable the conception of novel molecules that function as effective and selective pro-oxidants against specific targets. Full article

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article

Scaffolds designed for mechanically demanding soft tissue engineering applications should integrate mechanical support, efficient mass transfer, and good cellular compatibility. This work presents a one-pot method based on “radical-free click chemistry + carbodiimide coupling” to produce a double-network (DN) PEG–alginate cryogel. The PEG network is formed by a Michael addition reaction between thiol-based crosslinker and 8-arm PEG-acrylate. The second network is covalently crosslinked through EDC/NHS-mediated coupling of carboxyl groups in alginate and adipic acid dihydrazide (AAD). The subsequent freezing and gelation of the gel precursor at sub-zero temperatures results in an ice templated cryogel with an interconnected macroporous network. These cryogels demonstrate high elasticity, compressive modulus and rapid swelling equilibrium in aqueous environments, as well as controlled degradation under physiological conditions. Compared to the classical Ca²⁺ ion crosslinking systems, the covalent linking of the alginate in the double-network cryogel shows advantages in mechanical and structural stability. In addition, it is cell-compatible and allows culture of mesenchymal stem cells (MSCs) with homogeneous infiltration. Furthermore, the double-network cryogels supports chondrogenic differentiation of MSCs upon treatment with chondrogenic media or macrophage-conditioned media for a short period of time. These results indicate that crosslinking chemistry and polymer composition can be used to modulate the balance between mechanical performance and degradation behavior, while maintaining cytocompatibility and an interconnected macroporous network, thereby providing a scaffold design strategy for applications that require coordinated mechanical support and mass transfer, such as cartilage-related tissue engineering. Full article

Alternating glycopolymers bearing periodically arranged pendant carbohydrate residues were synthesized by reversible addition–fragmentation chain transfer (RAFT) copolymerization of maltose-containing vinyl ether (MalVE) and ethyl maleimide (EtMI). The resulting trithiocarbonate-terminated polymers were subsequently converted into thiol-terminated glycopolymers through post-polymerization end-group transformation. These structurally well-defined alternating glycopolymers were immobilized onto gold nanoparticles (AuNPs) via Au–S interactions to construct glycopolymer-functionalized glycointerfaces. Surface functionalization of the AuNPs was confirmed by an increase in hydrodynamic diameter from approximately 42 to 59 nm after polymer immobilization. The resulting glycopolymer-functionalized AuNPs exhibited concentration-dependent lectin-mediated aggregation behavior in the presence of concanavalin A, accompanied by characteristic red shifts and broadening of the localized surface plasmon resonance (LSPR) band arising from multivalent carbohydrate–lectin interactions at the nanoparticle interface. Although the apparent association constants obtained for free alternating glycopolymers using fluorescently labeled lectin cannot be directly compared with those obtained from LSPR-based aggregation assays of AuNP-immobilized glycopolymers, the values increased from the order of 10⁵ L mol⁻¹ in solution to the order of 10⁷ L mol⁻¹ at the nanoparticle interface. This trend suggests that immobilization onto AuNPs enhances multivalent carbohydrate–lectin interactions through multivalent presentation of the glycopolymer chains at the nanoparticle interface. As a control experiment, peanut agglutinin (PNA), which does not recognize maltose residues, was added to the glycopolymer-functionalized AuNPs. No significant LSPR shift or spectral broadening was observed, indicating that nanoparticle aggregation was not induced by nonspecific lectin addition but arose from specific interactions between maltose residues and Con A. Quantitative analysis suggested that polymer chain length may influence the aggregation behavior. These results demonstrate that alternating glycopolymers provide a useful platform for constructing sequence-regulated glycointerfaces and for investigating multivalent biomolecular interactions at nanoparticle surfaces. Full article

The exact mechanisms of skin involvement in type 1 diabetes (DM1) remain poorly understood. This study aimed to evaluate the relationship between antioxidants, oxidative stress, protein glycation, and glycoxidation, as well as matrix metalloproteinase (MMP) activity, in the skin of rats with DM1, while investigating whether insulin administration improves skin homeostasis. Male Wistar rats were assigned to three groups: control, diabetes, and diabetes treated with insulin. Significantly higher expression of GSH (gluthatione) and GSH-Px (glutathione peroxidase), elevated levels of AGE (Advanced Glycation End products), DT (dityrosine), KN (kynurenine), NFKN (N-formylkynurenine) and ONOO- (peroxynitrite), as well as increased activity of GLU (β-D-glucuronidase), NADPH oxidase (NOX) and MMP-1, -2, -3, -7, -9, -11 and -13 were observed in the skin of rats with DM1. Insulin treatment normalizes the skin’s antioxidant barrier and eliminates oxidative stress. It also reduces the intensity of protein glycation and glycoxidation, though not to the levels observed in the control group. Summarizing, in diabetic skin there is a complex interaction between the thiol antioxidant barrier, oxidative damage, protein glycation and glycoxidation as well as MMP expression. Insulin restores physiological balance in skin cells; however, glycation and ECM remodeling are still more pronounced than in healthy skin. Full article

Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg/kg) mitigates cadmium-induced toxicity (5 mg/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (−30.8%), elevated transaminases (AST, ALT; p < 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p < 0.01). Sperm concentration dropped from 75.2 to 21.8 × 10⁶/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 × 10⁶/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver/kidney biomarkers showed significant but incomplete recovery (p < 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (−8.4 kcal/mol), CAT (−8.3 kcal/mol), and SOD (−6.4 kcal/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery. Full article

Cotton fabrics are widely used due to their comfort and biodegradability; however, their intrinsic hydrophilicity limits their performance in advanced applications. In this work, a fluorine-free approach for imparting durable hydrophobicity to cotton was developed based on thiol-ene crosslinking of polysiloxane networks formed on the fiber surface. Two thiol-functional polysiloxanes differing in –SH group content were combined with four vinyl-functional organosilicon crosslinkers under UV (2,2-dimethoxy-2-phenylacetophenone (DMPA)) and thermal (2,2′-azobis(2-methylpropionitrile) (AIBN)) initiation. FT-IR analysis confirmed the presence of siloxane structures, while SEM-EDS revealed stable silicon- and sulfur-containing layers. SEM observations showed continuous coatings without blocking the textile structure. Water contact angle (WCA) measurements demonstrated that hydrophobic performance strongly depends on thiol content and crosslinker structure, with the highest values obtained for the thiol-rich polysiloxane and tetrafunctional vinyl crosslinker. All modified fabrics exhibited high durability, with minimal changes in WCA and complete droplet stability (1800 s) after washing. In the case of the lower-functionality polysiloxane, an increase in hydrophobicity after washing was observed, attributed to the reorganization of siloxane chains. These results demonstrate that thiol-ene crosslinking provides an effective strategy for designing durable, fluorine-free hydrophobic coatings on cotton. Full article