Melatonin-Nitric Oxide Crosstalk in Plants and the Prospects of NOMela as a Nitric Oxide Donor.

Melatonin regulates vital physiological processes in animals, such as the circadian cycle, sleep, locomotion, body temperature, food intake, and sexual and immune responses. In plants, melatonin modulates seed germination, longevity, circadian cycle, photoperiodicity, flowering, leaf senescence, postharvest fruit storage, and resistance against biotic and abiotic stresses. In plants, the effect of melatonin is mediated by various regulatory elements of the redox network, including RNS and ROS. Similarly, the radical gas NO mediates various physiological processes, like seed germination, flowering, leaf senescence, and stress responses. The biosynthesis of both melatonin and NO takes place in mitochondria and chloroplasts. Hence, both melatonin and nitric oxide are key signaling molecules governing their biological pathways independently. However, there are instances when these pathways cross each other and the two molecules interact with each other, resulting in the formation of N-nitrosomelatonin or NOMela, which is a nitrosated form of melatonin, discovered recently and with promising roles in plant development. The interaction between NO and melatonin is highly complex, and, although a handful of studies reporting these interactions have been published, the exact molecular mechanisms governing them and the prospects of NOMela as a NO donor have just started to be unraveled. Here, we review NO and melatonin production as well as RNS-melatonin interaction under normal and stressful conditions. Furthermore, for the first time, we provide highly sensitive, ozone-chemiluminescence-based comparative measurements of the nitric oxide content, as well as NO-release kinetics between NOMela and the commonly used NO donors CySNO and GSNO.

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

Trimethoxyphenyl containing compounds: Synthesis, biological evaluation, nitric oxide release, modeling, histochemical and histopathological studies.

Novel series of trimethoxy phenyl containing chalcone 3, 5, 6, 7, pyrazoline 4a&b, 9a-h and pyrazole 10a&b scaffolds were designed and synthesized. They were characterized by spectral data and elemental analyses. All newly synthesized compounds were screened for their in vitro COX-1/COX-2 inhibitory activities and in vivo anti-inflammatory activity. All the target compounds showed COX-2 inhibitory activity over COX-1. Compound 5c was the most active derivative with higher COX-2 inhibitory activity (IC50 = 0.039 µM) than celecoxib (IC50 = 0.045 µM), and selectivity index value of 321.28 nearly equal to that of celecoxib (S.I. = 326.66). Four additional derivatives 5a, 6, 8b and 9f exhibited excellent COX-2 inhibitory activity (IC50 = 0.041 - 0.049 µM) if compared to the reference drug, celecoxib, with selectivity index values (S.I. = 230.61 - 278.05). Additionally, prolonged in vivo A.I activity was observed in compounds 9e, 9 g, 10a and 10b with % inhibition ranged from 33.21 to 44.52%, after 7 h from carrageenan injection. Compound 9e appeared normal without degeneration similar to celecoxib as resulted from histolopathogical study. Compounds containing NO releasing moieties, 7, 10a and 10b were assesses to overcome the gastrointestinal side effects. Molecular modeling study was operated and achieved a parallel correlation with in vitro COX-2 assay results. Pharmacokinetic study for all the prepared compounds was developed.

Delivery of Nitric Oxide in the Cardiovascular System: Implications for Clinical Diagnosis and Therapy.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in the cardiovascular system, clinical applications centered on NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process, based on computational modeling and flow-mediated dilation, to assess endothelial function and vulnerability of atherosclerotic plaque. Then, emerging bioimaging technologies that have the potential to experimentally measure arterial NO concentration were discussed, including Raman spectroscopy and electrochemical sensors. In addition to diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the NO release platform to treat endothelial dysfunction and atherosclerosis and inhaled NO therapy to treat pulmonary hypertension and COVID-19. Two potential methods to improve the effectiveness of existing NO therapy were also discussed, including the combination of NO release platform and computational modeling, and stem cell therapy, which currently remains at the laboratory stage but has clinical potential for the treatment of CVD.

Chemical Constituents and their Antioxidant, Anti-Inflammatory and Anti-Acetylcholinesterase Activities from Pholidota cantonensis.

Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC50 = 0.72 ± 0.08 µM) than the positive control quercetin (IC50 = 12.94 ± 0.08 µM). Compound 13 also had a higher inhibitory rate (99.59 ± 0.43%) on AChE than that of the positive control galantamine (78.32 ± 1.16%) at the concentrate of 50 µg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs.

A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms.

BACKGROUND: Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. RESULTS: In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. CONCLUSIONS: Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

Curcumane C and (±)-curcumane D, an unusual seco-cadinane sesquiterpenoid and a pair of unusual nor-bisabolane enantiomers with significant vasorelaxant activity from Curcuma longa.

A new seco-cadinane sesquiterpenoid (curcumane C, 1) and a pair of new nor-bisabolene enantiomers [(+)- and (-)-curcumane D, 2a and 2b] were isolated from C. longa. Compound 1 possesses an unusual 4,5-seco-cadinane skeleton with a tetrahydrophthalide moiety, while 2a and 2b contain an unusual 15-nor-bisabolene skeleton with a chromone core. All compounds exhibited significant vasorelaxant effects against KCl-induced contraction of rat aortic rings. Compound 1 also exhibited a vasorelaxant effect against phenylephrine-induced contraction of rat aortic rings. Meanwhile, compound 1 showed a stronger vasorelaxant effect in endothelium-intact rat aortic rings compared with endothelium-denuded rat aortic rings, indicating that vasodilation by 1 involved both endothelium-dependent and endothelium-independent pathways. Furthermore, compound 1 increased the NO content in human umbilical vein endothelial cells and its vasorelaxant effect could be attenuated by treatment with L-NAME, an endothelium NO synthase inhibitor. Thus, the underlying vasodilatory mechanisms of 1 may be mediated via abrogation of extracellular Ca2+ influx and regulation of NO release in vascular endothelial cells.

Anti-Inflammatory Dembranoids from the Soft Coral Lobophytum crassum.

Abstract: Cembrane-type diterpenoids are among the most frequently encountered natural products from the soft corals of the genus Lobophytum. In the course of our investigation to identify anti-inflammatory constituents from a wild-type soft coral Lobophytumcrassum, two new cembranoids, lobophyolide A (1) and B (2), along with five known compounds (3-7), were isolated. The structures of these natural products were identified using NMR and MS spectroscopic analyses. Compound 1 was found to possess the first identified α-epoxylactone group among all cembrane-type diterpenoids. The in vitro anti-inflammatory effect of compounds 1-5 was evaluated. The results showed that compounds 1-5 not only reduced IL-12 release, but also attenuated NO production in LPS-activated dendritic cells. Our data indicated that the isolated series of cembrane-type diterpenoids demonstrated interesting structural features and anti-inflammatory activity which could be further developed into therapeutic entities.

Nitro-linolenic acid is a nitric oxide donor.

Nitro-fatty acids (NO2-FAs), which are the result of the interaction between reactive nitrogen species (RNS) and non-saturated fatty acids, constitute a new research area in plant systems, and their study has significantly increased. Very recently, the endogenous presence of nitro-linolenic acid (NO2-Ln) has been reported in the model plant Arabidopsis thaliana. In this regard, the signaling role of this molecule has been shown to be key in setting up a defense mechanism by inducing the chaperone network in plants. Here, we report on the ability of NO2-Ln to release nitric oxide (NO) in an aqueous medium with several approaches, such as by a spectrofluorometric probe with DAF-2, the oxyhemoglobin oxidation method, ozone chemiluminescence, and also by confocal laser scanning microscopy in Arabidopsis cell cultures. Jointly, this ability gives NO2-Ln the potential to act as a signaling molecule by the direct release of NO, due to its capacity to induce different changes mediated by NO or NO-related molecules such as nitration and S-nitrosylation or by the electrophilic capacity of these molecules through a nitroalkylation mechanism.

Sensitization of NO-Releasing Ruthenium Complexes to Visible Light.

We report a combined spectroscopical-theoretical investigation on the photosensitization of transition metal nitrosyl complexes. For this purpose, ruthenium nitrosyl complexes based on tetradentate biscarboxamide ligands were synthesized. A crystal structure analysis of a lithium-based ligand intermediate is described. The Ru complexes have been characterized regarding their photophysical and nitric oxide (NO) releasing properties. Quantum chemical calculations have been performed to unravel the influence of the biscarboxamide ligand frame with respect to the molecular electronic properties of the NO-releasing pathway. A quantitative measure for the ligand design within photosensitized Ru complexes is introduced and evaluated spectroscopically and theoretically by using time-dependent density functional theory.

X-ray Radiation-Controlled NO-Release for On-Demand Depth-Independent Hypoxic Radiosensitization.

Multifunctional stimuli-responsive nanotheranostic systems are highly desirable for realizing simultaneous biomedical imaging and on-demand therapy with minimized adverse effects. Herein, we present the construction of an intelligent X-ray-controlled NO-releasing upconversion nanotheranostic system (termed as PEG-USMSs-SNO) by engineering UCNPs with S-nitrosothiol (R-SNO)-grafted mesoporous silica. The PEG-USMSs-SNO is designed to respond sensitively to X-ray radiation for breaking down the S-N bond of SNO to release NO, which leads to X-ray dose-controlled NO release for on-demand hypoxic radiosensitization besides upconversion luminescent imaging through UCNPs in vitro and in vivo. Thanks to the high live-body permeability of X-ray, our developed PEG-USMSs-SNO may provide a new technique for achieving depth-independent controlled NO release and positioned radiotherapy enhancement against deep-seated solid tumors.

Influence of alkanolamine plasmas on poly(ethylene terephthalate) fibrous biomaterial constructs.

The development of fibrous polymer scaffolds is highly valuable for applications in tissue engineering. Furthermore, there is an extensive body of literature for chemical methods to produce scaffolds that release nitric oxide. However, these methods often use harsh chemistries and leave behind bulk waste. Alkanolamine low-temperature plasma (LTP) is unexplored and single-step processing to form nitric oxide (NO) releasing constructs is highly desirable. The major question addressed is whether it is possible to achieve single-step processing of spun polyester with alkanolamine plasma to achieve nitric oxide releasing capabilities. Herein we report the experiments, processes, and data that support the claim that it is indeed possible to produce such a bio-functional material for potential biomedical applications, especially in cardiovascular implants. Among the tested alkanolamines, monoethylamine (MEA) plasma treated biomaterial outperformed in comparison with diethanolamine (DEA) and triethanolamine (TEA) in terms of NO release and cellular response.

The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors.

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

Impact of uniaxial cyclic stretching on matrix-associated endothelial cell responses.

Uniaxial cyclic stretching plays a pivotal role in the fields of tissue engineering and regenerative medicine, influencing cell behaviors and functionality based on physical properties, including matrix morphology and mechanical stimuli. This study delves into the response of endothelial cells to uniaxial cyclic strain within the geometric constraints of micro-nano fibers. Various structural scaffold forms of poly(l-lactide-co-caprolactone) (PLCL), such as flat membranes, randomly oriented fiber membranes, and aligned fiber membranes, were fabricated through solvent casting and electrospinning methods. Our investigation focuses on the morphological variation of endothelial cells under diverse geometric constraints and the mechanical-dependent release of nitric oxide (NO) on oriented fibrous membranes. Our results indicate that while uniaxial cyclic stretching promotes endothelial cell spreading, the anisotropy of the matrix morphology remains the primary driving factor for cell alignment. Additionally, uniaxial cyclic stretching significantly enhances NO release, with a notably stronger effect correlated to the increasing strain amplitude. Importantly, this study reveals that uniaxial cyclic stretching enhances the mRNA expression of key proteins, including talin, vinculin, rac, and nitric oxide synthase (eNOS).

Preliminary investigation of nitric oxide release from upconverted nanoparticles excited at 808 nm near-infrared for brain tumors.

Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

Hydroxypropyl methylcellulose reinforced bilayer hydrogel dressings containing L-arginine-modified polyoxometalate nanoclusters to promote healing of chronic diabetic wounds.

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.

Chemical composition and the anti-inflammatory effect of volatile compounds from Anaxagorea luzonensis A. Gray.

Anaxagorea luzonensis A. Gray, a member of the Annonaceae family, has been used to treat a variety of illnesses for a long time. For the first time, A. luzonensis volatile compounds (ALVCs) were extracted from the leaves, and the components were identified using gas chromatography-mass spectrometry (GC-MS). Further, the main compositions of ALVCs were also assessed for their ability to bind with anti-inflammatory proteins using a docking model. In addition, in vitro tests e.g. inhibition of protein degradation and the inhibition of nitric oxide release using RAW264.7 macrophage cells were utilized for evaluating the anti-inflammatory activity. The results showed that the principal compounds of ALVCs were bulnesol (34.1 %), cubitene (17.8 %), ß-eudesmol (10.4 %), epi-longipinanol (5.9 %), and (Z)-nerolidyl acetate (5.5 %). Three compounds viz. bulnesol, cubitene, and ß-eudesmol bound firmly to cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), as shown by the in silico analysis, similar to the positive control diclofenac. ALVCs effectively inhibited protein degradation with the IC50 of 31 ± 2.3 µg/mL and inhibited nitric oxide production with the IC50 of 43.30 ± 3.37 µg/mL. These findings showed that ALVCs might have a promising anti-inflammatory effect by blocking several inflammatory proteins.

Near Infrared-Triggered Nitric Oxide-Release Nanovesicles with Mild-Photothermal Antibacterial and Immunomodulation for Healing MRSA-Infected Diabetic Wounds.

Bacterial infection-induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near-infrared (NIR)-triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR-activatable methylene blue (MB) polypeptide-assembled nanovesicle (Au/PEL-PBA-MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on-demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) at temperatures < 49.7 °C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA-induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA-infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.

NIR-triggered NO production combined with photodynamic therapy for tumor treatment.

Photodynamic therapy (PDT), as one of the most promising cancer therapy methods, is still limited by several drawbacks, such as tissue hypoxia and shallow light penetration of blue-violet light (200-450 nm), and red light (750 nm) is more penetrating to tissues than blue-violet light, but still lower than near-red light (750-1350 nm). Therefore, we proposed a synergistic therapy system by combining the near-infrared light-triggered PDT with nitric oxide (NO)-based gas therapy to enhance the anti-tumor effects. Upconversion nanoparticles (UCNPs) were loaded with the photosensitizers of ZnPc and the NO donors of l-arginine (L-Arg) to obtain the nanocomposites of UCN@mSiO2@ZnPc@L-Arg. Under 980 nm laser irradiation, reactive oxygen species (ROS) could be produced for PDT and react with l-Arg to produce NO, which is previously reported to have a greater killing effect on tumor cells than ROS and also plays an important role in promoting PDT in our study. Both the in vitro and in vivo tests demonstrated that the combined therapy of PDT with NO therapy could enhance the tumor killing effect significantly compared with the unique application of PDT. The UCNPs-based nanocomposites are expected to be widely used in biomedicine for tumor inhibition.

A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing.

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N'-dis-sec-butyl-N, N'-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.