Carbon Monoxide Release Research Articles

Fire behavior of furfurylated paulownia wood

ABSTRACT Wood is an aesthetically pleasing, sustainable material for various uses. All materials, including wood, are intended to be long-lasting, maintaining their original appearance. The effects of furfurylation on the fire characteristics of wood are still unclear, even though it significantly increases the dimensional stability, hardness, and biodegradation resistance of wood. This study aimed to evaluate the fire characteristics of furfurylated wood. Thermogravimetric analysis showed that the time required for the infiltration of furfuryl alcohol into the samples significantly exceeded the values commonly reported in the literature. The results obtained by measurements on a cone calorimeter indicate that furfurylation significantly increases peak values of heat release rate, carbon monoxide, carbon dioxide, and smoke production in the phase immediately after the initiation. On the contrary, carbon-monoxide (CO) production decreased in the phase of heterogeneous combustion of carbonaceous residue.

MILITARY ECOCIDE IN UKRAINE AS A DESTRUCTIVE CONSEQUENCE OF THE USE OF RUSSIAN MISSILES AND PROJECTILES

Effectively, russia’s aggression against Ukraine can be considered the first case of intentional ecocide during wartime in this century. Through its actions, russia has caused massive destruction of the animal and plant world, pollution of the atmosphere, Ukrainian fertile lands, and water resources. According to calculations by the working group at the State Environmental Inspection, as of January 2023, the ecological damage to Ukraine during the 11 months of russian military aggression amounts to over 1 trillion 743 billion hryvnias, or over 47.6 billion dollars. This sum includes hundreds of thousands of square kilometers of ruined soil and devastated lands, forest fires, emissions of poisonous substances into the atmosphere, destruction of animals, alterations to the migratory paths of birds, and more. The top five regions most affected by ecocide in Ukraine are Dnipropetrovsk, Kharkiv, Mykolaiv, Donetsk, and Zaporizhzhia regions.
 The study of war ecocide crimes allows to systematise them by the following features: air pollution, soil pollution, destruction of green spaces, destruction of wildlife, water pollution, unauthorized use of subsoil, and disruption of ecosystems Since the beginning of the full-scale armed aggression by russian occupation forces on objects within the 71 territory of Ukraine, almost 6,500 missile strikes and nearly 3,500 aerial strikes have been carried out, resulting in environmental damage.
 Missiles launched onto Ukrainian territory carry hundreds and thousands of kilograms of chemical substances. In case of complete combustion and dispersion of remnants into the surrounding environment, they pose significant pollution and are toxic to all living beings.
 The destruction of the upper fertile layer of soil, which has been forming over centuries, occurs as a result of missile explosions, artillery shells of various types, cluster bombs, drones, mines, and various types of multiple rocket launchers.
 A significant problem is the contamination of soil with chemical substances, leading to a reduction in fertility and causing harm to both humans and animals living in polluted areas. In substantial areas of Ukraine, there is considerable damage to the surface layer of the soil due to the burning of munitions. The detonation of missiles, artillery shells, cluster bombs results in the release of carbon monoxide, carbon dioxide, water vapor, nitrogen oxides, formaldehyde, hydrogen cyanide, nitrogen, as well as a large amount of toxic organic compounds, which then enter the soil.
 According to assessments from the Kyiv School of Economics and Zoï Environment Network, a total of 186,000 km2 of land, nearly 31% of Ukraine's territory, is at risk of damage and pollution. Among them, over 20,000 km2 are damaged by more than 75% In addition to missiles, the aggressor country employs projectiles of various calibers and cluster bombs, the detonation of which causes environmental destruction, including damage to buildings, structures, industrial facilities, soil, wildlife, and ecosystems. Ukrainian land has transformed into a horrifying testing ground for various types of weaponry, including long-range artillery, salvo fire systems, phosphorus bombs, and guided missiles.
 A threatening issue is the replacement of territories, particularly agricultural lands. A mined area loses its intended purpose and cannot be utilized for a long period. Additionally, the demining of such territory requires substantial expenses.
 Therefore, russian missiles and projectiles pose a deadly threat to humans, animals, plants, harm the environment, devastate soil, water bodies, forests, destroy infrastructure, alter landscapes, and dismantle ecosystems.
 Thus, the investigation of war ecocide crimes involving russian missiles and projectiles allows the conclusion that these are extremely harmful actions resulting from military aggression. Those who perpetrate them are well aware of the serious and irreversible long-term damage inflicted on the environment.

Structure-Photoreactivity Relationship Study of Substituted 3-Hydroxyflavones and 3-Hydroxyflavothiones for Improving Carbon Monoxide Photorelease.

Carbon monoxide (CO) is notorious for its toxic effects but is also recognized as a gasotransmitter with considerable therapeutic potential. Due to the inherent challenges in its delivery, the utilization of organic CO photoreleasing molecules (photoCORMs) represents an interesting alternative to CO administration characterized by high spatial and temporal precision of release. This paper focused on the design, synthesis, and photophysical and photochemical studies of 20 3-hydroxyflavone (flavonol) and 3-hydroxyflavothione derivatives as photoCORMs. Newly synthesized compounds bearing various electron-donating and electron-withdrawing groups show bathochromically shifted absorption maxima and considerably enhanced CO release yields compared to the parent unsubstituted flavonol, exceeding 0.8 equiv of released CO in derivatives exhibiting excited states with a charge-transfer character. Until now, such outcomes have been limited to flavonol derivatives possessing a π-extended aromatic system. In addition, thione analogs of flavonols, 3-hydroxyflavothiones, show substantial bathochromic shifts of their absorption maxima and enhanced photosensitivity but provide lower yields of CO formation. Our study elucidates in detail the mechanism of CO photorelease from flavonols and flavothiones, utilizing steady-state and time-resolved spectroscopies and photoproduct analyses, with a particular emphasis on unraveling the structure-photoreactivity relationship and understanding competing side processes.

Investigating the Combined Toxicity of Cu(II) and Carbon Monoxide (CO); Cellular CO Delivery Using a Cu(II) Flavonolato Complex.

Carbon monoxide (CO) delivery molecules are of significant current interest as potential therapeutics, including for anticancer applications. A recent approach toward generating new types of materials-based anticancer agents involves combining the Fenton reactivity of a redox active metal ion with CO delivery. However, small molecule examples of these types of entities have not been systematically studied to evaluate the combined effect on cellular toxicity. Herein we describe a Cu(II) flavonolato complex which produces anticancer effects through a combination of copper-mediated reactive oxygen species (ROS) generation and light-induced flavonol CO release. Confocal microscopy studies provide evidence of enhanced flavonol uptake in the copper flavonolato system relative to the free flavonol, which leads to an increased amount of CO delivery within cells. Importantly, this work demonstrates that a metal flavonolato species can be used to produce enhanced toxicity effects resulting from both metal ion-induced Fenton reactivity and increased cellular uptake of a flavonol CO donor.

Multimodal Carbon Monoxide Photorelease from Flavonoids.

Photooxygenation of flavonoids leads to the release of carbon monoxide (CO). Our structure-photoreactivity study, employing several structurally different flavonoids, including their 13C-labeled analogs, revealed that CO can be produced via two completely orthogonal pathways, depending on their hydroxy group substitution pattern and the reaction conditions. While photooxygenation of the enol 3-OH group has previously been established as the CO liberation channel, we show that the catechol-type hydroxy groups of ring B can predominantly participate in photodecarbonylation.

Effect of Liquid Glass-Modified Lignin Waste on the Flammability Properties of Biopolyurethane Foam Composites.

Water-blown biopolyurethane (bioPUR) foams are flammable and emit toxic gases during combustion. Herein, a novel approach suggested by the current study is to use different amounts of lignin waste (LigW), which increases the thermal stability and delays the flame spread and sodium silicate (LG), which has foaming ability at high temperatures and acts as a protective layer during a fire. However, there have been no studies carried out to investigate the synergy between these two materials. Therefore, two different ratios, namely 1/1 and 1/2 of LigW/LG, were used to prepare bioPUR foam composites. The obtained bioPUR foam composites with a 1/2 ratio of LigW/LG exhibited inhibition of flame propagation during the ignitability test by 7 s, increased thermal stability at higher temperatures by 40 °C, reduced total smoke production by 17%, reduced carbon monoxide release by 22%, and increased compressive strength by a maximum of 123% and 36% and tensile strength by a maximum of 49% and 30% at 100 °C and 200 °C, respectively, compared to bioPUR foam composites with unmodified LigW. Additionally, thanks to the sufficient compatibility between the polymeric matrix and LigW/LG particles, bioPUR foam composites were characterised by unchanged or even improved physical and mechanical properties, as well as increased glass transition temperature by 16% compared to bioPUR foam composites with unmodified LigW particles, making them suitable for application as a thermal insulating layer in building envelopes.

Cigarette smoking and urinary bladder cancer: The danger alarm is screaming!

The cancer of urinary bladder is a very common cause of cancer related mortality all over the world and approximately more than half patients suffering from bladder cancer had been smokers. In addition to this, in such patients the cancer is more intense, higher in grade and stage and does not respond well to chemotherapy (Jin et al., 2017). Cigarette smoking is a major risk factor for respiratory and extra respiratory cancers in human body. While the oral and lung cancer result on account of direct contact with the tobacco products, the urinary bladder mucus membrane is exposed to a number of metabolites of tobacco products and if this exposure is sustained for a longer duration, a deadly cancer results (Omare et al., 2022). Over 7000 chemical compounds have been found in tobacco smoke and more than 50 of these have been a labelled as carcinogenic. When tobacco burns, it releases carbon monoxide, benzene, formaldehyde and polycyclic aromatic hydrocarbons (PAH), hydrogen, cyanide, nitrosamine, etc. Recent studies have shown that the bladder cancer patients who have been smoker have been found to have altered metabolanomics of urinary bladder epithelium in variety of ways. Firstly, some metabolites of tobacco create hyper methylation while many types of nitrosamines and nicotine metabolites create genotoxicity resulting in DNA damage, DNA adducts, mutations and ultimately carcinogenesis (Jin et al., 2017; Fuller et al., 2028; Suzuki et al., 2020). Some years ago, an impression was created that if one uses electronic cigarettes, the incidence of urinary bladder cancer can be lowered, but recent studies have refuted that (Fuller et al., 2028). Although tobacco industry is exploring to create less toxic types of tobacco, but the danger of high grade, urinary bladder cancer is still looming large on humanity (Stephen and Hatsukami, 2022) and therefore, one must respond to this alarm. The temptation to adopt smoking is increasing in younger population in developing countries and therefore not only a greater emphasis on laboratory and clinical research is needed but also a wide spread campaign on social media to warn people about the association of cigarette smoking and bladder cancer are the need of hour. Tobacco addiction in various forms is not confined to a particular group, strata, or gender. Every year, ‘World No Tobacco Day” is celebrated on May 31st to draw attention to the adverse effects of tobacco consumption. Despite being labeled as a potent carcinogen and the health risks associated with it, people find it difficult to get out of tobacco addiction. Similarly, there are numerous other toxic substances used daily that are directly linked to health issues like allergies, infertility, birth defects, learning disabilities, different types of cancers, and several more. Across the world, extensive research is being conducted on Environmental Health Toxicology to assess the adverse effects of various chemicals on human health. Journal of Environmental Biology publishes research on different aspects of Environmental Sciences, Biological Sciences and Toxicology, however, to expand our horizon we now provide a forum for Medical and Pharmaceutical researchers to showcase their research pertinent to Toxicants and their impact on human and animal health. ournal of Environmental Biology is of interest to toxicologist, pharmacologist, zoologist, botanist, ecologist, environmental scientist, industry R&D organizations and others engaged in environmental research and consultation. We welcome new submissions (Original Research Articles, Research Reviews & Case Studies) from researchers working in the areas of Environmental Health Toxicology and also encourage scientists to curate Theme-based Special Issues.

Red light-triggered release of ROS and carbon monoxide for combinational antibacterial application.

The abuse of antibiotics has led to the emergence of a wide range of drug-resistant bacteria. To address the challenge of drug-resistant bacterial infections and related infectious diseases, several effective antibacterial strategies have been developed. To achieve enhanced therapeutic effects, combinational treatment approaches should be employed. With this in mind, a metal-organic framework (MOF) based nanoreactor with integrated photodynamic therapy (PDT) and gas therapy which can release reactive oxygen species (ROS) and carbon monoxide (CO) under red light irradiation has been developed. The release of ROS and CO under red light irradiation exerts a preferential antibacterial effect on Gram-positive/Gram-negative bacteria. The bactericidal effects of ROS and CO on Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) are better than ROS only, showing a combinational antibacterial effect. Furthermore, the fluorescence emission properties of porphyrin moieties can be leveraged for real-time tracking and imaging of the nanoreactors. The simple preparation procedures of this material further enhance its potential as a versatile and effective antibacterial candidate, thereby presenting a new strategy for PDT and gas combinational treatment.

Synthesis, structural characterization, docking studies and bioactivities of carbon monoxide release molecules based on triphenylphosphonium-glycyrrhetinic acid derivatives

Carbon monoxide-releasing molecules (CORMs) containing cobalt complexes based on triphenylphosphonium-glycyrrhetinic acid (GA-TPP) were synthesized. This includes cytotoxicity, mitochondrial apoptosis, molecular docking, as well as western blotting.

Visible-Light-Activated Carbon Monoxide Release from Porphyrin-Flavonol Hybrids.

We report on porphyrin-flavonol hybrids consisting of a porphyrin antenna and four covalently bound 3-hydroxyflavone (flavonol) groups, which act as highly efficient photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs). These bichromophoric systems enable activation of the UV-absorbing flavonol chromophore by visible light up to 650 nm and offer precise spatial and temporal control of CO administration. The physicochemical properties of the porphyrin antenna system can also be tuned by inserting a metal cation. Our computational study revealed that the process occurs via endergonic triplet-triplet energy transfer from porphyrin to flavonol and may become feasible thanks to flavonol energy stabilization upon intramolecular proton transfer. This mechanism was also indirectly supported by steady-state and transient absorption spectroscopy techniques. Additionally, the porphyrin-flavonol hybrids were found to be biologically benign. With four flavonol CO donors attached to a single porphyrin chromophore, high CO release yields, excellent uncaging cross sections, low toxicity, and CO therapeutic properties, these photoCORMs offer exceptional potential for their further development and future biological and medical applications.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

RSS and ROS Sequentially Activated Carbon Monoxide Release for Boosting NIR Imaging‐Guided On‐Demand Photodynamic Therapy

AbstractCarbon monoxide shows great therapeutic potential in anti‐cancer. In particular, the construction of multifunctional CO delivery systems can promote the precise delivery of CO and achieve ideal therapeutic effects, but there are still great challenges in design. In this work, a RSS and ROS sequentially activated CO delivery system is developed for boosting NIR imaging‐guided on‐demand photodynamic therapy. This designed system is composed of a CO releaser (BOD‐CO) and a photosensitizer (BOD‐I). BOD‐CO can be specifically activated by hydrogen sulfide with simultaneous release of CO donor and NIR fluorescence that can identify H2S‐rich tumors and guide light therapy, also depleting H2S in the process. Moreover, BOD‐I generates 1O2 under long‐wavelength light irradiation, enabling both PDT and precise local release of CO via a photooxidation mechanism. Such sequential activation of CO release by RSS and ROS ensured the safety and controllability of CO delivery, and effectively avoided leakage during delivery. Importantly, cytotoxicity and in vivo studies reveal that the release of CO combined with the depletion of endogenous H2S amplified PDT, achieving ideal anticancer results. It is believed that such theranostic nanoplatform can provide a novel strategy for the precise CO delivery and combined therapy involved in gas therapy and PDT.

Simultaneous Light-Triggered Release of Nitric Oxide and Carbon Monoxide from a Lipid-Coated Upconversion Nanosystem Inhibits Colon Tumor Growth.

Gas therapy has gained noteworthy attention in biomedical research, with the rise of gas-releasing molecules enhancing their therapeutic potential, especially when integrated into nano-based drug delivery systems. Herein, we present a lipid-coated gas delivery system to simultaneously shuttle two gas-releasing molecules carrying nitric oxide (NO) and carbon monoxide (CO), respectively. Upconversion nanoparticles (UCNPs) are designed to generate photons at 360 nm upon 808 nm of near-infrared (NIR) irradiation. These in situ-generated UV photons trigger simultaneous NO and CO release from S-nitrosoglutathione (GSNO) and the CO-releasing molecule (CORM), respectively, which are coloaded into lipid-coated UCNP/GSNO/CORM/FA nanoparticles (LUGCF). LUGCF with a GSNO/CORM mass ratio of 2:1 is determined to be optimal in terms of synergistically instigating apoptosis in HCT116 and CT26 colon cancer cells, where both NO/CO are released and subsequent production of ROS are detected. This CO/NO combination nanoplatform exhibits a very effective inhibition of colon tumor growth in vivo at relatively low doses upon a mild 808 nm irradiation. Overall, we effectively integrated two therapeutic gas-releasing molecules in one NIR-responsive nanosystem, presenting a promising therapeutic strategy for future biomedical applications in dual-gas cancer therapy.

Investigating the thermal behavior of acyclovir

Viruses are a significant health, economic and social issue. Acyclovir (ACV) is an antiviral agent analogous to the guanine nitrogenous base that acts by interrupting the multiplication of DNA of virus in infected cells. The thermal decomposition mechanism of ACV was evaluated by thermoanalytical techniques Thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA), evolved gas analysis by thermogravimetry coupled to vibrational infrared spectrometry in gas phase (TG-FTIR), differential scanning calorimetry (DSC), hot stage microscopy (HSM) and mass spectrometry (MS). TG/DTG and DTA curves were performed under N2 and air atmospheres. Under N2, four stages of mass loss were observed from the TG curve between 523-1273 K, while under air decomposition occurred in a similar way, however, the additional burning of carbonaceous material was found in air. DSC curves were obtained in heat-cool-heat mode, from 233 to 543 K, under N2 atmosphere and presented two endothermic peaks related to water loss and phase transition followed by exothermic crystallization of a new form, followed by melting associated with decomposition in agreement with HSM images. Powder X-ray diffraction (PXRD) profiles confirmed the phase transitions. From the TG-FTIR characterization, it was suggested that decomposition undergoes by release of water, 1,3-dioxolane, isocyanic acid, carbon dioxide, carbon monoxide, and ammonia. MS spectrum of the residue collected at 543 K revealed the presence of guanine free base as decomposition product in agreement with the release of dioxolane ring in gas phase.

Preparation and characterization of UiO‐66‐NH2 adsorbed triethyl phosphate: Flame retardancy and smoke suppression for epoxy resins

AbstractThe zirconium‐based metal–organic framework material (UiO‐66‐NH2) was synthesized by solvothermal method, and its excellent adsorption performance was used to combine it with the phosphorus‐based flame retardant triethyl phosphate (TEP) and to improve the flame retardant and smoke suppression properties of epoxy resin (EP). The morphology, chemical composition, and structure of the synthesized flame retardant were analyzed by scanning electron microscope, energy dispersion spectrum, Fourier transform infrared spectroscopy, and x‐ray diffractometer. The cone calorimeter measurement of EP composite materials shows that EP composite materials have good flame retardant and smoke suppression properties. Compared with EP, after the UiO‐66‐NH2 flame retardant which adsorbs TEP is added, the peak heat release rate, total heat release, peak smoke release rate, total smoke production, carbon monoxide release rate, and carbon dioxide release rate of EP composites have been reduced. From the results of thermal analysis and scanning electron microscope, it can be seen that the synthesized flame retardant can act both in the condensed phase and in the gas phase. Thereby, the combustion of the matrix and the diffusion of the toxic gas, smoke and heat generated during the combustion are inhibited, and the flame retardant and smoke suppression effects are achieved.Highlights Make full use of the excellent adsorption performance of MOF. TEP was fully adsorbed in UiO‐66‐NH2 pores. UiO‐66‐NH2 in synergy with TEP improves EP flame retardancy.

A Single-Component Dual Donor Enables Ultrasound-Triggered Co-release of Carbon Monoxide and Hydrogen Sulfide.

The development of dual gasotransmitter donors can not only provide robust tools to investigate their subtle interplay under pathophysiological conditions but also optimize therapeutic efficacy. While conventional strategies are heavily dependent on multicomponent donors, we herein report an ultrasound-responsive water-soluble copolymer (PSHF) capable of releasing carbon monoxide (CO) and hydrogen sulfide (H2 S) based on single-component sulfur-substituted 3-hydroxyflavone (SHF) derivatives. Interestingly, sulfur substitution can not only greatly improve the ultrasound sensitivity but also enable the co-release of CO/H2 S under mild ultrasound irradiation. The co-release of CO/H2 S gasotransmitters exerts a bactericidal effect against Staphylococcus aureus and demonstrates anti-inflammatory activity in lipopolysaccharide-challenged macrophages. Moreover, the excellent tissue penetration of ultrasound irradiation enables the local release of CO/H2 S in the joints of septic arthritis rats, exhibiting superior therapeutic efficacy without the need for any antibiotics.

Construction of bismuth oxide iodide (BiOI)/zinc titanium oxide (Zn2TiO4) p-n heterojunction nanofibers with abundant oxygen vacancies for improving photocatalytic carbon dioxide reduction

The conversion of carbon dioxide (CO2) into value-added syngas represents an effective approach for addressing both environmental issues and carbon neutrality issue. However, the slow charge dynamics and low CO2 affinity severely limit the photocatalytic CO2 reduction reaction. In this study, bismuth oxide iodide (BiOI)/zinc titanium oxide (Zn2TiO4) composite nanofibers were successfully prepared by immobilizing BiOI nanosheets on Zn2TiO4 electrospun nanofibers through a solvothermal reaction method. The results of photocatalytic research indicate that the BiOI/Zn2TiO4 composite nanofibers exhibit improved photocatalytic activity in CO2 reduction compared to pristine BiOI nanosheets and Zn2TiO4 nanofibers. The highest carbon monoxide (CO) release rate of BiOI/Zn2TiO4 nanofibers could reach 9.10 µmol‧g−1‧h−1, which is 18.6 times and 6.6 times higher than that of pristine BiOI nanosheets and Zn2TiO4 nanofibers, respectively. The enhanced photocatalytic activity can be credited to the formed BiOI/Zn2TiO4 p-n heterojunction, which can boost electron separation, reduce charge recombination at the interface, and promote the reaction process. The presence of oxygen vacancies in BiOI/Zn2TiO4 nanofibers can not only provide active site to facilitate the adsorption and activation of CO2 molecules, but also adjust the energy band structure of the catalyst to accelerate carriers transfer. After four cycles of testing, the CO release rate of BiOI/Zn2TiO4 nanofibers remains nearly constant, demonstrating its excellent stability. This work develops a feasible strategy to improve the efficiency of photoreduction of CO2 through energy band engineering and surface defect technology.

Dual-switched carbon monoxide nano gas tank for auto-diagnosis and precision therapy of osteoarthritis

Carbon monoxide (CO) has great potential in the therapy of osteoarthritis (OA), but its controllable delivery in vivo is still an intractable problem. To optimize CO gas therapy for OA, a stable CO release platform with multi-stimulus responsiveness must be designed. Herein, we describe a local delivery system (Fe3(CO)12 @Croc-PEG5K) for near-infrared fluorescence (NIRF) imaging-guided photothermal treatment and CO gas synergistic therapy. As a nano gas tank, Fe3(CO)12 @Croc-PEG5K releases CO on-demand under near infrared (NIR) laser irradiation, scavenges free radicals and regulates the pH in the OA microenvironment, and relieves the inflammatory response of macrophages to maintain the vitality of chondrocytes. Furthermore, the pH-dependent NIRF imaging properties of Fe3(CO)12 @Croc-PEG5K can be exploited to determine the administration interval and auto-monitor the curative effects during the therapeutic process. Owing to these merits, the photothermal and CO gas synergistic therapy mediated by Fe3(CO)12 @Croc-PEG5K can be optimized to deliver outstanding therapeutic performance in vivo, as demonstrated by the OA rat model. Our study is the first to validate the therapeutic effect of CO against OA in vivo, reveals a promising strategy for precision medicine pertaining to the treatment of OA and broadens the scope of CO gas therapy.

Carbon monoxide release from ultrasound-sensitive microbubbles improves endothelial cell growth.

Carbon monoxide is a gasotransmitter that may be beneficial for vascular tissue engineering and regenerative medicine strategies because it can promote endothelial cell (EC) proliferation and migration by binding to heme-containing compounds within cells. For example, CO may be beneficial for vascular cognitive impairment and dementia because many patients' disrupted blood-brain barriers do not heal naturally. However, control of the CO dose is critical, and new controlled delivery methods need to be developed. This study developed ultrasound-sensitive microbubbles with a carefully controlled precipitation technique, loaded them with CO, and assessed their ability to promote EC proliferation and function. Microbubbles fabricated with perfluoropentane exhibited good stability at room temperature, but they could still be ruptured and release CO in culture with application of ultrasound. Microbubbles synthesized from the higher boiling point compound, perfluorohexane, were too stable at physiological temperature. The lower-boiling point perfluoropentane microbubbles had good biocompatibility and appeared to improve VE-cadherin expression when CO was loaded in the bubbles. Finally, tissue phantoms were used to show that an imaging ultrasound probe can efficiently rupture the microbubbles and that the CO-loaded microbubbles can improve EC spreading and proliferation compared to control conditions without microbubbles as well as microbubbles without application of ultrasound. Overall, this study demonstrated the potential for use of these ultrasound-sensitive microbubbles for improving blood vessel endothelialization.

Exploring the therapeutic potential of a nano micelle containing a carbon monoxide-releasing molecule for metabolic-associated fatty liver disease by modulating hypoxia-inducible factor-1α.

Metabolic-associated fatty liver disease (MAFLD) encompasses a spectrum of chronic liver diseases, including steatohepatitis, cirrhosis, and liver cancer. Despite the increasing prevalence and severity of MAFLD, no approved pharmacological interventions are currently available. Hypoxia-inducible factor-1α (HIF-1α) has emerged as a crucial early mediator in the pathogenesis of MAFLD. Previously, we demonstrated the potent anti-inflammatory properties of the nano-designed carbon monoxide (CO) donor, styrene maleic acid copolymer (SMA) encapsulating CO-releasing molecule (SMA/CORM2), which effectively suppressed HIF-1α in various inflammatory disorders. Here, we investigated the therapeutic potential of SMA/CORM2 in a mouse model of MAFLD induced by a high-fat methionine- and choline-deficient (HF-MCD) diet. Following 4 weeks of HF-MCD diet consumption, we observed pronounced hepatic lipid accumulation accompanied by disrupted lipid metabolism, polarization of macrophages towards the pro-inflammatory M1 phenotype, activation of the NLRP3 inflammasome, and upregulation of the TGF-β fibrosis signaling pathway. Notably, the early and upstream event driving these pathological changes was the upregulation of HIF-1α. Treatment with SMA/CORM2 (10mg/kg, three times per week) led to a significant increase in CO levels in both the circulation and liver, resulting in remarkable suppression of HIF-1α expression even before the onset of apparent pathological changes induced by the HF-MCD diet. Consequently, SMA/CORM2 administration exerted a significantly protective and therapeutic effect on MAFLD. In vitro studies using hepatocytes treated with high concentrations of fatty acids further supported these findings, as knockdown of HIF-1α using short hairpin RNA (shRNA) elicited similar effects to SMA/CORM2 treatment. Collectively, our results highlight the therapeutic potential of SMA/CORM2 in the management of MAFLD through suppression of HIF-1α. We anticipate that SMA/CORM2, with its ability to modulate HIF-1α expression, may hold promise for future applications in the treatment of MAFLD. STATEMENT OF SIGNIFICANCE: Carbon monoxide (CO) is a crucial gaseous signaling molecule that plays a vital role in maintaining homeostasis and is a potential target for treating many inflammatory diseases. Developing drug delivery systems that can deliver CO stably and target specific tissues is of great interest. Our team previously developed a nano micellar CO donor, SMA/CORM2, which exhibits superior bioavailability to native CORM2 and shows therapeutic potential in many inflammatory disease models. In this study, we showed that SMA/CORM2, through controlled CO release, significantly ameliorated steatohepatitis and liver fibrosis induced by an HF-MCD diet by suppressing an HIF-1α mediated inflammatory cascade. These findings provide new insight into the anti-inflammatory function of CO and a promising approach for controlling metabolic-associated fatty liver disease.