Hydroxypropyl-β-cyclodextrin/hyaluronic acid modified polydopamine nanoparticles co-loaded with BNN6 and epirubicin for synergistic photothermal/gas/chemotherapy of breast cancer.

One-step synthesized NIR-responsive polydopamine nanoparticles for synergistic nitric oxide chemotherapy and photothermal therapy against multidrug-resistant bacteria.

Glioblastoma is the most common primary malignant brain tumor with poor prognosis. The immunosuppressive microenvironment and cancer stem cells (CSCs) drive therapeutic resistance. The role of nitric oxide (NO) metabolism in coordinating glioma stemness and immune evasion remains unclear. We performed multi-omics analysis using CGGA, TCGA, and Rembrandt datasets (n=1500) and single-cell RNA sequencing (n=65,655cells). PRMT1 was identified as a key NO metabolism-associated prognostic gene through Cox regression and LASSO modeling. Validation used glioma cell lines, patient-derived GSCs, and orthotopic mouse models. NO metabolism activity increased with glioma grade and correlated with poor survival (p<0.001). Single-cell analysis showed positive correlation between NO metabolism and stemness (R=0.35, p<0.001). High-NO metabolism tumors showed M0 macrophage enrichment (p<0.001) and M1 depletion (p<0.05). PRMT1 expression was elevated in high-grade gliomas and correlated with NOS2 (R=0.26-0.46, p<0.001). PRMT1 knockdown reduced proliferation (76%), colony formation (75%), and CD133+ cells (11.74% to 3.11%). NO donor treatment rescued knockdown effects. In vivo PRMT1 silencing reduced tumor growth to 35% of controls (p<0.001) and decreased SOX2 and PD-L1 expression. PRMT1 links NO metabolism to glioma stemness and immunosuppression by regulating stemness factors (OCT4, SOX2) and immune checkpoints (PD-L1) through NO-dependent mechanisms. PRMT1 represents a therapeutic target that could disrupt stem cell populations and remodel the immunosuppressive microenvironment.

Magnetic/photothermal dual-driven micro/nanorobots for synergistic NO-mediated photothermal thrombolysis.

Nitric oxide (NO) is a widespread signaling molecule which has far-reaching effects in cellular physiology and pathophysiology, especially in cancer biology. Its actions are concentration-dependent where low concentrations facilitate tumor development and high concentrations cause cytotoxicity. NO alters several cancer hallmarks, affecting the initiation, progression, immune evasion, and therapeutic responses of tumors via cGMP-dependent and -independent pathways. Various cell types in the tumor microenvironment (TME) produce NO in a concentration gradient creating a strong concentration gradient that forms the immune landscape. NO mediates immunosuppression through the regulation of tumor-associated macrophage, myeloid-derived suppressor cell, T cells, and natural killer cells. It also controls angiogenesis and normalization of the vasculature via the VEGF-NO axis. Moreover, NO effects epithelial-mesenchymal transition and metastasis concentration-dependently. Notably, NO exists in a complex interaction with gasotransmitters, and it interacts with hydrogen sulfide and carbon monoxide in crosstalk to control cancer biology. Therapeutic interventions that focus on NO e.g., NO donors, iNOS-inhibitors and nanodelivery systems have been promising in preclinical practice. Nevertheless, clinical translation is complicated by the fact that the concentrations of intratumoral NO have to be tightly controlled, safety issues exist, and there are not many biomarkers of patient stratification. Integration of NO-based therapies with immunotherapy and precision medicine approaches holds promise for enhancing treatment outcomes. Continued research spanning chemical, biological, and clinical domains is crucial for unlocking the full therapeutic potential of NO in cancer.

Targeted microwave sensitizers reprogram cancer-associated fibroblasts via nitric oxide delivery to potentiate hepatocellular carcinoma therapy.

Novel anticancer paeonol derivatives possessing a nitric oxide donor moiety as TrxR inhibitors: design, synthesis, biological evaluation.

JOURNAL/mgres/04.03/01612956-990000000-00095/figure1/v/2026-05-14T124239Z/r/image-tiff Dysregulation of the nitric oxide/nitric oxide synthase system is consistently observed in the aftermath of traumatic brain injury. It plays a pivotal yet paradoxical role in traumatic brain injury progression. Moreover, the modulation of the altered nitric oxide/nitric oxide synthase homeostasis via inhaled nitric oxide, nitric oxide donors, nitric oxide synthase inhibitors, and indirect methods such as mild hypothermia and medical gases in the brain, both during and after traumatic brain injury, can exert a significant impact on the clinical outcome. This review integrates current findings from preclinical studies and clinical trials to elucidate the dynamic contributions of nitric oxide to traumatic brain injury pathophysiology and to highlight emerging interventions targeting nitric oxide-related pathways. While physiological nitric oxide levels support cerebral blood flow and neuroprotection, excessive production via nitric oxide synthase isoforms (especially inducible nitric oxide synthase) drives secondary injury through cytotoxicity, edema, and blood-brain barrier disruption. Therapeutic strategies targeting nitric oxide pathways, including inhaled nitric oxide, nitric oxide donors, and specific nitric oxide synthase inhibitors like VAS203, show significant neuroprotective potential in preclinical models, though clinical translation remains limited.

Furoxan derivatives with antimalarial activity that disrupt P. falciparum endoplasmic reticulum calcium homeostasis.

Controlled nitric oxide (NO) release within deep periodontal pockets remains a critical unmet need for effective periodontitis therapy, as conventional approaches are plagued by poor targeting, uncontrolled release, and limited deep-tissue penetration. Herein, we engineer sonosensitized hemoglobin nanoparticles (PH-SNO) using heme as an endogenous sonosensitizer and S-nitrosothiol (SNO) as a robust NO donor, enabling ultrasound (US)-mediated synergistic gas-sonodynamic therapy for periodontitis. Upon US irradiation, PH-SNO simultaneously generates reactive oxygen species (ROS) via heme and triggers S-NO bond cleavage for on-demand NO release; ROS and NO further react to form peroxynitrite, exerting potent oxidative-nitrosative stress. This dual effect eradicates major periodontal pathogens, disrupts biofilms, abrogates NF-κB signaling and NLRP3 inflammasome activation, and downregulates pro-inflammatory cytokines. In vivo studies confirm that PH-SNO/US alleviates gingival inflammation, suppresses osteoclast activity, preserves alveolar bone, and promotes tissue repair with excellent biocompatibility, providing a safe, noninvasive, and translatable nonantibiotic therapeutic strategy for periodontitis.

Wound management remains a significant clinical challenge due to bacterial infection, oxidative stress, and inflammation. To address these issues, we developed a multifunctional hydrogel, NO-GM/Fle@FD, by combining gelatin methacryloyl (GelMA), Pluronic F127 diacrylate (F127DA), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and the antibiotic fleroxacin (Fle). The hydrogel allows rapid photopolymerization under 405nm light, forming a robust network with controlled NO release and localized antibiotic delivery. In infected murine wound model, NO-GM/Fle@FD accelerated wound closure through three mechanisms: (1) infection suppression via fleroxacin-mediated bactericidal activity, (2) ROS scavenging to reduce oxidative damage, and (3) inflammatory modulation through sustained NO release. Histological analysis revealed complete re-epithelialization by day 10, reduced inflammation, and enhanced collagen deposition in the NO-GM/Fle@FD group. Immunofluorescence showed decreased IL-1β (pro-inflammatory) and increased IL-10 (anti-inflammatory), confirming the hydrogel's ability to resolve inflammation and counteract oxidative stress. This study demonstrates that NO-GM/Fle@FD effectively targets the infection-oxidative stress-inflammation triad, providing a promising therapeutic solution for treating infectious wounds, diabetic ulcers, burns, and other chronic complex wounds.

Nanosheets doped collagen‑based composite sponge dressing with integrated negative pressure wound therapy, photothermal, and gas therapies for wound healing.

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.

Nitric oxide interplay with hydrogen sulfide modulates gene expression and photosystem II function through enhanced antioxidant defense under PEG-induced osmotic stress in common bean (Phaseolus vulgaris L.).

Heat stress is a major abiotic factor limiting plant growth and productivity. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, plays an important role in regulating plant responses to abiotic stress. This study investigated the effects of SNP application on growth parameters, total chlorophyll content, and oxidative stress indicators in Capsicum annuum L. seedlings grown under high temperature conditions. Plants were grown at 25 °C (control) and 38 °C (heat stress) and treated with 50 and 100 µM SNP. The results showed that heat stress reduced growth parameters and total chlorophyll content, while increasing lipid peroxidation (MDA) and hydrogen peroxide (H₂O₂) accumulation. Heat stress enhanced catalase (CAT) activity. Under heat stress, 50 µM SNP alleviated oxidative damage by reducing MDA and H₂O₂ levels, whereas 100 µM SNP increased these parameters. In contrast, SNP application suppressed CAT activity in a dose-dependent manner. These findings indicate that SNP induces dose-dependent physiological and biochemical responses in Capsicum annuum L. seedlings under heat stress and that appropriate SNP doses may contribute to mitigating heat stress–induced damage. The results may also support the development of dose based stress management strategies for sustainable crop production under high temperature conditions.

A metal-ion coordination-promoted transition from a closed-shell singlet (CSS) form of an NNO donor ligand to an open-shell triplet (OST) and open-shell singlet (OSS) forms has been disclosed. Ruthenium(II) complexes of 2-(((2-((5-nitropyridin-2-yl)amino)phenyl)imino)methyl)phenol (L1H2), which is a source of both aminyl and phenoxyl radicals, have been explored. 2e- oxidized [L12--2e-] form of L12- is either a CSS quinoid (L1Q) or an open-shell diradical (L1dirad) incorporating aminyl and phenoxyl radicals. The OST form of L1dirad is presented by (L1dirad)S=1, while the OSS form is abbreviated by (L1dirad)S=0. Ruthenium(II) complexes cis-[RuII(L1dirad)(PPh3)Cl2] (1) and trans-[RuII(L12-)(PPh3)2(CO)] (2) were successfully isolated. L1Q is the ground electronic state of the noncoordinated [L12--2e-] form, while in 1, L1dirad form has been stabilized. 1·CH2Cl2 is superparamagnetic at 2 K due to the (L1dirad)S=1 form and diamagnetic at above 50 K stabilizing the (L1dirad)S=0 form. Broken symmetry, BS (1,1) density functional theory calculations infer that OST with (L1dirad)S=1 form, is the ground electronic state of 1, while OSS with (L1dirad)S=0 form, is the excited state. The OST form of the frozen matrix of 1 at 5 K has been authenticated by the X-band EPR signals at g = 4.325-3.070 and 2.074-1.377. The powder spectrum at 5 K also displays signals at g = 3.516 and 2.385-1.840. 1 exhibits an NIR double excitation transition at 700-1100 nm. Similar to 1, 22+ is a L1dirad complex of ruthenium(II) authenticated by BS DFT calculations and reveals a double excitation transition at 400-600 nm.

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.

Garlic-released NO and H2S modulate Arabidopsis metabolism by reshaping redox balance and redox-dependent post-translational modifications.

The therapeutic efficacy against triple-negative breast cancer (TNBC) is often limited by poor nanodrug penetration through the dense extracellular matrix (ECM). Although sonodynamic therapy (SDT) offers a non-invasive approach with deep tissue penetration, its effectiveness using wide-bandgap sonosensitizers is constrained by rapid electron-hole recombination. Guided by AI-driven screening, we developed narrow-bandgap (1.0-1.5eV) tin monosulfide (SnS) as a sonosensitizer, which was further engineered into a cascade reaction-enhanced sonodynamic therapeutic system by loading nitric oxide (NO) donors and modifying with polyethylene glycol (PEG). Upon ultrasound stimulus, this system generates both ROS and NO, which not only exert the cytotoxic effects of sonodynamic therapy but also combine to yield highly cytotoxic peroxynitrite (ONOO-). The resulting ONOO- activates matrix metalloproteinases (MMPs) to degrade the ECM, thereby enhancing nanoparticle penetration and establishing a self-reinforcing antitumor cycle. Furthermore, this ultrasound-driven strategy simultaneously induces mitochondrial apoptosis via ROS, overcoming the depth limitations of conventional light-based therapies and presenting a potent approach for TNBC treatment.