Functional modification of gum Arabic with nitric oxide donor: Coating characterization with modulation of antioxidant defence and membrane integrity in lemons.

Sex differences in mitochondrial Ca2+ during ischemia/reperfusion injury: A role for S-Nitrosylation.

Hospital acquired infections (HAIs) remain a prevailing issue in clinical settings. These challenges are associated with the health and economic burdens of complications such as bloodstream infections, biomedical device fouling, and antimicrobial resistance. Nitric oxide (NO) is an endogenous gasotransmitter that has vasodilatory, antimicrobial, and antiplatelet effects. This has allowed NO to surface as a potential bioactive strategy for integration into medical device technologies. When combined with other surface modifications, such as liquid infusion (LI) and copper nanoparticles(CuNPs), this approach yields slippery, antifouling surfaces with dual antibacterial and NO-catalysis properties. Herein, we combined S-nitroso-N-acetylpenicillamine (SNAP), a promising nitric oxide donor that releases NO at physiological levels for 7 days in the presence of heat and light, with catalytic tuning via CuNPs with a LI polymeric surface. In addition, SNAP Cu LI samples exhibited minimal donor leaching and slippery behavior with sliding angles of <20° across a 7-day test period. These propertiesof NO support its antimicrobial and antiplatelet effects in addition to enhanced catalysis induced by metal-donor interactions. This eradicates microorganisms such as methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli with >99.8% and 98.7% reduction in bacterial cell viability, respectively. In addition, LI reduced blood protein adsorption by >80% and prevented platelet activation by >72%. By integrating nitric oxide-releasing silicone rubber with copper nanoparticles and a liquid-infused layer, these surface modifications produce a multifunctional medical device surface with antibacterial, antithrombotic, and antifouling capabilities.

Based on two key pathological features of pulmonary arterial hypertension (PAH), elevated pulmonary artery pressure and vascular remodeling, two new series of nitric oxide (NO) donating lenumlostat derivatives were designed, synthesized, and biologically evaluated. The results indicated that compound LNO 9 exhibited LOXL2 inhibitory activity comparable to lenumlostat, remarkably suppressing hypoxia-induced collagen oxidation and aberrant collagen cross-linking. Furthermore, LNO 9 effectively released NO and increased 3',5'-cyclic guanosine monophosphate in HPASMCs, thereby exerting a potent vasodilation. In both hypoxia- and MCT-induced rat models of PAH, LNO 9 significantly improved right ventricular hypertrophy and pulmonary arterial medial wall thickness. Meanwhile, LNO 9 demonstrated superior efficacy in reducing right ventricular systolic pressure compared to lenumlostat. In short, the present study has demonstrated unequivocally that a therapeutic approach for PAH that combines NO donors for vasodilation with extracellular matrix inhibitors to suppress vascular remodeling represents a promising treatment.

Nitric oxide (NO) treated radioresistant tumors by relieving hypoxia and blocking DNA repair, but its nonselective toxicity has precluded therapeutic use. Here, we introduce a radioresistant tumor-selective NO nanogenerator that releases NO exclusively within the irradiated field. We identified BNN6 as a uniquely radiosensitive NO donor and loaded it into Glucose-Regulated Protein 78 (GRP78)-targeted nanocarrier to obtain PBTN, exploiting the overexpression of GRP78 in radioresistant cancers for selective accumulation. Upon irradiation, BNN6 undergoes one-electron reduction to release NO exclusively within the irradiated volume. NO combines radiation-induced reactive oxygen species to form peroxynitrite, provoking tumor DNA breaks while simultaneously suppressing DNA repair. In CT26 tumor-bearing mice, the combination of radiotherapy with PBTN and anti-PDL1 antibody achieved a tumor growth suppression of 96.5% and 80% survival at 40 days post-treatment. This tumor-targeted, irradiation-triggered NO nanogenerator thus offers a safe, precise, and translatable strategy to overcome radioresistance.

Orthopaedic implants require surfaces that resist bacterial colonisation while supporting host cell compatibility. In this study, we fabricated highly interconnected porous titanium (Ti) foams using a cost‑effective sintering-dissolution process (SDP) and functionalised them with 11‑aminoundecyltriethoxysilane (AUTES) and covalently tethered N-diazeniumdiolate nitric oxide (NO) donors. Structural characterisation by Scanning electron microscopy, X‑ray micro‑CT, and Brunauer-Emmett-Teller analyses confirmed a hierarchical porous architecture with ~ 73% total porosity and extensive internal surface area, enabling efficient chemical functionalisation. Chemiluminescence analysis demonstrated formulation‑dependent NO payloads and sustained release for over 15h in bacterial culture medium. The NO‑releasing foams significantly reduced biofilm-associated Escherichia coli and Staphylococcus aureus compared with untreated controls, with the 20% AUTES/NO formulation showing the most persistent antibiofilm activity at 24h (p < 0.05). Limited effects were observed against planktonic bacteria. Human mesenchymal stem cells (hMSCs) adhered to and remained viable on both unmodified and functionalised foams over 7days, indicating cytocompatibility of the surface modification following NO release. These findings demonstrate that SDP-derived porous Ti foams can be functionalised for localised NO delivery and effective antibiofilm activity while maintaining initial hMSC compatibility, offering a scalable platform for multifunctional Ti-based implant surfaces.

Nitroso-Containing Pharmaceuticals: Targets, Pharmacological Activities, and Their Metabolic Mechanisms.

Gas therapy shows significant clinical promise for antimicrobial applications by effectively modulating bacterial activity and suppressing biofilm formation. Nevertheless, the limited gas release efficiency continues to pose a major challenge that compromises its therapeutic effectiveness. Here, we designed and constructed a multilayer nanocomposite (HBAC) using hollow polydopamine (HPDA) as the primary carrier for the nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-di-nitroso-p-phenylenediamine (BNN6). By grafting gold nanocages (Au NCs) onto its surface, the photothermal conversion efficiency (PCE, η) was significantly enhanced, optimizing the real-time NO release. Furthermore, leveraging the hollow structure and nanoenzyme activity of Au NCs, we encapsulated the antimicrobial agent curcumin (Cur), enabling HBAC to simultaneously activate three synergistic antibacterial modes: gene-like inhibition, photothermal therapy (PTT), and photodynamic therapy (PDT) under near-infrared laser irradiation. This multifunctional platform exhibits exceptional efficacy in suppressing the growth and biofilm formation of diverse Gram-positive and Gram-negative bacteria, including S. epider, E. coli, B. subt, and E. aero, with a bactericidal efficiency exceeding 95%. Our approach offers a promising strategy to enhance gas sterilization efficiency and accelerate the clinical translation of multimodal antimicrobial therapy.

ABSTRACT Light‐activatable nitric oxide (NO) donors are promising for precision cancer therapy but are hindered by premature leakage and a reliance on high dosages that may lead to off‐target cytotoxicity. Herein, we report a near‐infrared (NIR)‐gated nanogenerator (Cy‐NO NPs) engineered for low‐dose, NO‐potentiated multi‐modal cancer phototherapy. By anchoring a thiol‐functionalized ortho‐trifluoromethyl‐nitroaromatic moiety onto a cyanine (IR825) scaffold, the design ensures negligible NO leakage under oxidative, reductive, and thermal stresses, thereby eliminating systemic toxicity. Upon 808 nm excitation, the excited‐state energy dissipation is balanced to drive four concurrent pathways: (i) a photoinduced intramolecular electron transfer (PIET) process triggering a nitro‐to‐nitrite rearrangement for NO release; (ii) Type I &amp; II photodynamic effects; (iii) photothermal conversion; and (iv) NIR‐II fluorescence emission. The released NO reacts in situ with simultaneous superoxide (O 2 •− ) bursts to yield highly cytotoxic peroxynitrites (ONOO − ). This synergistic ROS/RNS surge targets mitochondria, inducing membrane depolarization and rapid ATP depletion to trigger apoptosis. Guided by NIR‐II fluorescence imaging, this multi‐modal therapy achieves efficient tumor ablation in vivo, validating a potent low‐dose strategy for integrating controlled gas release with phototherapy.

Light-activatable nitric oxide (NO) donors are promising for precision cancer therapy but are hindered by premature leakage and a reliance on high dosages that may lead to off-target cytotoxicity. Herein, we report a near-infrared (NIR)-gated nanogenerator (Cy-NO NPs) engineered for low-dose, NO-potentiated multi-modal cancer phototherapy. By anchoring a thiol-functionalized ortho-trifluoromethyl-nitroaromatic moiety onto a cyanine (IR825) scaffold, the design ensures negligible NO leakage under oxidative, reductive, and thermal stresses, thereby eliminating systemic toxicity. Upon 808nm excitation, the excited-state energy dissipation is balanced to drive four concurrent pathways: (i) a photoinduced intramolecular electron transfer (PIET) process triggering a nitro-to-nitrite rearrangement for NO release; (ii) Type I & II photodynamic effects; (iii) photothermal conversion; and (iv) NIR-II fluorescence emission. The released NO reacts in situ with simultaneous superoxide (O2 •-) bursts to yield highly cytotoxic peroxynitrites (ONOO-). This synergistic ROS/RNS surge targets mitochondria, inducing membrane depolarization and rapid ATP depletion to trigger apoptosis. Guided by NIR-II fluorescence imaging, this multi-modal therapy achieves efficient tumor ablation in vivo, validating a potent low-dose strategy for integrating controlled gas release with phototherapy.

Hypocrellin A (HA), a photoactive perylenequinone from the bambusicolous Shiraia fungi, possesses potent photodynamic anticancer and antimicrobial properties. However, the signaling mechanisms governing its biosynthesis remain poorly understood. In this study, we identify spermidine (Spd), a ubiquitous polyamine, as a novel elicitor that significantly enhances HA production in Shiraia sp. S9. Spd activated both nitric oxide synthase (NOS) and nitrate reductase (NR) for nitric oxide (NO) generation, leading to the stimulation of the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling cascade. Inhibition of NO generation or sGC activity suppressed both cGMP accumulation and HA biosynthesis. Transcriptomic analysis revealed that Spd-induced NO signaling upregulated genes in central carbon metabolism and the hypocrellin biosynthetic gene cluster. The dual elicitation strategy by the combined addition of Spd and the NO donor sodium nitroprusside (SNP) exhibited a strong enhancing effect, increasing HA yield by 4.6-fold compared with control cultures. These results demonstrate that Spd regulates HA biosynthesis through a NO-cGMP-mediated signaling pathway, unveiling polyamines as new metabolic elicitors and providing an efficient dual-elicitation strategy for large-scale hypocrellin production.

Targeted therapeutic delivery for treating bacterial infections remains underutilized in most pharmaceutical interventions. Existing therapeutics (i.e., antibiotics) are often systematically administered despite the presence of localized infection, leading to both off-target toxicity and suboptimal bacterial clearance with limited efficacy against biofilms. The overuse of antibiotics has resulted in increased antimicrobial resistance, creating a need for alternative interventions that are unlikely to confer resistance. Nitric oxide (NO), an endogenous mediator produced by macrophages and other immune cells in response to infection, elicits broad spectrum antibacterial and antibiofilm activity. The use of exogenous NO donors, alone or as conjugated ligands to macromolecular scaffolds, has proven effective in treating anatomical targets, including dermal wounds, dental infections, and pulmonary conditions, in a localized manner. In this perspective, we provide an overview of the recent advancements in NO-releasing biomaterials, highlighting design strategy and antimicrobial action across diverse anatomical sites.

A novel macrophage membrane-camouflaged ultra-small copper sulfide and photothermal-responsive nitric oxide donor nanocomposites for enhanced synergistic antitumor therapy.

Single-pore silica nanotherapeutic platform with pH-Responsive NO release for osteoporosis repair.

Hypoxia-activated dual donors of H2S and NO alleviate myocardial injury in coronary heart disease via synergistic mechanisms.

CS-NO releasing hydrogel protects against neuron apoptosis and inflammation through suppressing the HIF-1α and MAPK pathway in stroke.

Bidirectional coupling of neuronal Ca2+ and nitric oxide signals visualized by a dual biosensor.

Nitric oxide (NO) plays a central role in wound healing, by regulating vascular homeostasis, inflammation, and antimicrobial effects. However, chronic diabetic wounds are difficult to heal due to the hyperglycemic microenvironment, which reduces endogenous NO production. Therefore, developing intelligent dressings capable of spatiotemporally programmed NO delivery holds great promise in promoting diabetic wound healing. Herein, we engineered an environmentally activatable hydrogel that enabled on-demand NO release for diabetic wound healing. The CS-SNAP hydrogel was achieved by covalent grafting of NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto the matrix of carboxymethyl chitosan methacryloyl (CMCSMA), and by subsequent fast photopolymerization during only 10 s. The CS-SNAP hydrogel enabled sustained release of NO over 300 min by simply modulating ambient light and temperature. When applied to diabetic wounds, not only did the CS-SNAP hydrogel exhibit effective antibacterial activity, but it also showed good angiogenic ability and promoted M1-to-M2 polarization of macrophages. Together, this environmentally activatable platform demonstrates great potential to shorten the inflammatory phase of diabetic wounds, prevent bacterial colonization, and accelerates diabetic wound healing.

A multifunctional hyaluronic acid- polyurethane foam with prolonged nitric oxide release: In-vitro evaluation for wound dressing applications.

S-nitrosylation of Dexras1 attenuates fear memory generalization in the infralimbic cortex.