Dual-Delivery Temperature-Sensitive Hydrogel with Antimicrobial and Anti-Inflammatory Brevilin A and Nitric Oxide for Wound Healing in Bacterial Infection.

Bacterial infections impede the wound healing process and can trigger local or systemic inflammatory responses. Therefore, there is an urgent need to develop a dressing with antimicrobial and anti-inflammatory properties to promote the healing of infected wounds. In this study, BA/COs/NO-PL/AL hydrogels were obtained by adding brevilin A (BA) camellia oil (CO) submicron emulsion and nitric oxide (NO) to hydrogels consisting of sodium alginate (AL) and Pluronic F127 (PL). The hydrogels were characterized through dynamic viscosity analysis, differential scanning calorimetry, and rheology. They were evaluated through anti-inflammatory, antimicrobial, and wound healing property analyses. The results showed that BA/COs/NO-PL/AL hydrogels were thermo-responsive and had good ex vivo and in vivo anti-inflammatory activity, and they also exhibited strong antimicrobial activity against methicillin-resistant Staphylococcus aureus Pseudomonas aeruginosa (MRPA) and methicillin-resistant Staphylococcus aureus (MRSA). They were able to effectively promote healing of the infected wound model and reduce inflammation and bacterial burden. H&E and Masson's staining showed that BA/COs/NO-PL/AL hydrogels promoted normal epithelial formation and collagen deposition. In conclusion, BA/COs/NO-PL/AL hydrogels are promising candidates for promoting the healing of infected wounds.

Hydrogen Bond Assisted Three-Component Tandem Reactions to Access N-Alkyl-4-Quinolones.

Hydrogen-bonding catalytic reactions have gained great interest. Herein, a hydrogen-bond-assisted three-component tandem reaction for the efficient synthesis of N-alkyl-4-quinolones is described. This novel strategy features the first proof of polyphosphate ester (PPE) as a dual hydrogen-bonding catalyst and the use of readily available starting materials for the preparation of N-alkyl-4-quinolones. The method provides a diversity of N-alkyl-4-quinolones in moderate to good yields. The compound 4h demonstrated good neuroprotective activity against N-methyl-ᴅ-aspartate (NMDA)-induced excitotoxicity in PC12 cells.

Bacteria-Adhesive Nitric Oxide-Releasing Graphene Oxide Nanoparticles for MRPA-Infected Wound Healing Therapy.

A bacteria-infected wound can lead to being life-threatening and raises a great economic burden on the patient. Here, we developed polyethylenimine 1.8k (PEI1.8k) surface modified NO-releasing polyethylenimine 25k (PEI25k)-functionalized graphene oxide (GO) nanoparticles (GO-PEI25k/NO-PEI1.8k NPs) for enhanced antibacterial activity and infected wound healing via binding to the bacterial surface. In vitro antibacterial activity and in vivo wound healing efficacy in an infected wound model were evaluated compared with NO-releasing NPs (GO-PEI25k/NO NPs). Surface modification with PEI1.8k can enhance the ability of nanoparticles to adhere to bacteria. GO-PEI25k/NO-PEI1.8k NPs released NO in a sustained manner for 48 h and exhibited the highest bactericidal activity (99.99% killing) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MRPA) without cytotoxicity to L929 mouse fibroblast cells at 0.1 mg/mL. In the MRPA-infected wound model, GO-PEI25k/NO-PEI1.8k NPs showed 87% wound size reduction while GO-PEI25k/NO NPs showed 23% wound size reduction at 9 days postinjury. Masson trichrome and hematoxylin and eosin staining revealed that GO-PEI25k/NO-PEI1.8k NPs enhanced re-epithelialization and collagen deposition, which are comparable to healthy mouse skin tissue. GO-PEI25k/NO-PEI1.8k NPs hold promise as effective antibacterial and wound healing agents.

Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages.

Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis.

Synthesis of novel 1-phenyl-benzopyrrolizidin-3-one derivatives and evaluation of their cytoneuroprotective effects against NMDA-induced injury in PC12 cells.

A range of novel 1-phenyl-benzopyrrolizidin-3-one derivatives were synthesized and evaluated for neuroprotective effects against N-methyl-ᴅ-aspartate (NMDA)-induced injury in PC12 cells. Interestingly, derivatives that 1-phenyl moiety bearing electron-donating group, especially benzyloxy, and the trans-forms exhibited better protective activity against NMDA-induced neurotoxicity. Compound 11 m demonstrated the best neuroprotective potency and shown a dose-dependent prevention. The increased intracellular calcium (Ca2+) influx caused by NMDA in PC12 cells was reversed in the case of compound 11 m pretreatment at 15 µM. These results suggested that the synthesized 1-phenyl-benzopyrrolizidin-3-one derivatives exerted neuroprotective effect on NMDA-induced excitotoxicity in PC12 cells associated with inhibition of Ca2+ overload and can be further optimized for the development of neuroprotective agents.

Tumor-Penetrable Nitric Oxide-Releasing Nanoparticles Potentiate Local Antimelanoma Therapy.

Although nitric oxide (NO) has been emerging as a novel local anticancer agent because of its potent cytotoxic effects and lack of off-target side effects, its clinical applications remain a challenge because of the short effective diffusion distance of NO that limits its anticancer activity. In this study, we synthesized albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles (Alb-PLP/NO NPs) that possess tumor-penetrating and NO-releasing properties for an effective local treatment of melanoma. Sufficient NO-loading and prolonged NO-releasing characteristics of Alb-PLP/NO NPs were acquired through PLGA-conjugated LP/NO copolymer (PLP/NO) synthesis, followed by nanoparticle fabrication. In addition, tumor penetration ability was rendered by the electrostatic adsorption of the albumin on the surface of the nanoparticles. The Alb-PLP/NO NPs showed enhanced intracellular NO delivery efficiency and cytotoxicity to B16F10 murine melanoma cells. In B16F10-tumor-bearing mice, the Alb-PLP/NO NPs showed improved extracellular matrix penetration and spatial distribution in the tumor tissue after intratumoral injection, resulting in enhanced antitumor activity. Taken together, the results suggest that Alb-PLP/NO NPs represent a promising new modality for the local treatment of melanoma.

Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds.

Nitric oxide (NO), a highly reactive and lipophilic molecule, is one of the molecules present in the wound environment and implicated as an important regulator in all phases of wound healing. Here, we developed an NO-releasing thermoresponsive hydrogel (GSNO-PL/AL) composed of S-nitrosoglutathione (GSNO), pluronic F127 (PL), and alginate (AL) for the treatment of infected wounds. The GSNO was incorporated into the thermoresponsive PL/AL hydrogel, and differential scanning calorimetry techniques were used for the hydrogel characterization. The hydrogel was assessed by in vitro NO release, antibacterial activity, cytotoxicity, and wound-healing activity. The GSNO-PL/AL hydrogel demonstrated thermal responsiveness and biocompatibility, and it showed sustained NO release for 7 days. It also exhibited potent bactericidal activity against Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative multidrug-resistant Pseudomonas aeruginosa (MRPA). Moreover, the GSNO-PL/AL treatment of MRPA-infected wounds accelerated healing with a reduced bacterial burden in the wounds. The GSNO-PL/AL hydrogel would be a promising option for the treatment of infected wounds.

Colitis-targeted hybrid nanoparticles-in-microparticles system for the treatment of ulcerative colitis.

Nanoparticle (NP)-based drug delivery systems accumulate in the disrupted epithelium of inflamed colon tissue in ulcerative colitis. However, premature early drug release and uptake or degradation of NPs during their passage through the harsh gastric or intestinal environment compromise their therapeutic outcomes. This study aimed to develop an advanced colitis-targeted hybrid nanoparticles-in-microparticles (NPsinMPs) drug delivery system to overcome the aforementioned challenges. First, sustained drug releasing poly(lactic-co-glycolic acid) NPs were generated and further encapsulated in pH-sensitive Eudragit FS30D MPs to ensure complete drug protection in a gastric-like pH and for selective delivery of NPs to the colon. SEM and confocal microscopy for the NPsinMPs revealed successful NP encapsulation. NPsinMPs prevented drug release in an acidic gastric-like and intestinal-like pH and presented a sustained release thereafter at an ileal and colonic pH, indicating the degradation of the outer pH-sensitive MPs and release of NPs. Furthermore, in vivo imaging of gastrointestinal tract of a colitis mouse orally administered with fluorescent NPsinMPs revealed higher fluorescence intensities selectively in the colon, demonstrating the release of loaded NPs and their concomitant accumulation at the site of colon inflammation. NPsinMPs markedly mitigated experimental colitis in mice indicated by improved histopathological analysis, decreased myeloperoxidase activity, neutrophils and macrophage infiltration, and expression of proinflammatory cytokines in colonic tissues compared with NP-treated mice. The present results show the successful formulation of an NPsinMP-based drug delivery system and provide a platform to improve NP-based colon-targeted drug delivery through improved protection of encapsulated NPs and their payload in the early small intestine.

Viriditoxin Stabilizes Microtubule Polymers in SK-OV-3 Cells and Exhibits Antimitotic and Antimetastatic Potential.

Microtubules play a crucial role in mitosis and are attractive targets for cancer therapy. Recently, we isolated viriditoxin, a cytotoxic and antibacterial compound, from a marine fungus Paecilomyces variotii. Viriditoxin has been reported to inhibit the polymerization of bacterial FtsZ, a tubulin-like GTPase that plays an essential role in bacterial cell division. Given the close structural homology between FtsZ and tubulin, we investigated the potential antimitotic effects of viriditoxin on human cancer cells. Viriditoxin, like paclitaxel, enhanced tubulin polymerization and stabilized microtubule polymers, thereby perturbing mitosis in the SK-OV-3 cell line. However, the morphology of the stabilized microtubules was different from that induced by paclitaxel, indicating subtle differences in the mode of action of these compounds. Microtubule dynamics are also essential in cell movement, and viriditoxin repressed migration and colony formation ability of SK-OV-3 cells. Based on these results, we propose that viriditoxin interrupts microtubule dynamics, thus leading to antimitotic and antimetastatic activities.

Nitric Oxide-Releasing S-Nitrosoglutathione-Conjugated Poly(Lactic-Co-Glycolic Acid) Nanoparticles for the Treatment of MRSA-Infected Cutaneous Wounds.

S-nitrosoglutathione (GSNO) has emerged as a potent agent for the treatment of infected cutaneous wounds. However, fabrication of GSNO-containing nanoparticles has been challenging due to its high hydrophilicity and degradability. The present study aimed to fabricate nanoparticles using newly synthesized GSNO-conjugated poly(lactic-co-glycolic acid) (PLGA) (GSNO-PLGA; GPNPs). Since hydrophilic GSNO was covalently bound to hydrophobic PLGA, loss of GSNO during the nanoparticle fabrication process was minimized, resulting in sufficient loading efficiency (2.32% of GSNO, 0.07 µmol/mg of NO). Real-time NO release analysis revealed biphasic NO release by GPNPs, including initial burst release within 3 min and continuous controlled release for up to 11.27 h, due to the differential degradation rates of the -SNO groups located at the surface and inside of GPNPs. Since GPNPs could deliver NO more efficiently than GSNO in response to increased interaction with bacteria, the former showed enhanced antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) at the same equivalent concentrations of NO. Finally, the facilitating effects of GPNPs on infected wound healing were demonstrated in MRSA-challenged full-thickness wound mouse model. Collectively, the results suggested GPNPs as an ideal nanoparticle formulation for the treatment of MRSA-infected cutaneous wounds.

Advances in colon-targeted nano-drug delivery systems: challenges and solutions.

Nano-drug delivery systems (NDDS) for colon-targeted drug delivery are an active area of research on local diseases affecting the colon, such as ulcerative colitis, Crohn's disease, colon cancer, and for the delivery of peptide or protein drugs and vaccinations. In particular, targeted nano-drug delivery to the colon is advantageous for colon-specific diseases because nanoparticles can accumulate in diseased parts, improve the efficacies of therapeutics, and enable localized treatments, which reduces systemic toxicity. However, there are many hurdles, such as burst drug release, enzyme and acidic degradation of drug and carrier in the stomach, pH variations, mucus entrapment, and systemic uptake in the upper small intestine, which could challenge and compromise the successful delivery of NDDS to the colon. With advancements in NDDS, it may be possible to overcome these challenges leading to efficient drug delivery for colon-specific disorders. This review describes a few of the potential colon-specific drug delivery areas and the challenges faced by colon-targeted orally administered delivery systems, and provides an updated summary of recent advances in the development of orally administered NDDS for colon targeting, and the future advances in this research.

Chitosan-based nitric oxide-releasing dressing for anti-biofilm and in vivo healing activities in MRSA biofilm-infected wounds.

Bacterial biofilms on wounds impair the healing process and often lead to chronic wounds. Chitosan is a well-known biopolymer with antimicrobial and anti-biofilm effects. S-nitrosoglutathione (GSNO) has been identified as a promising nitric oxide (NO) donor to defend against pathogenic biofilms and enhance wound healing activities. In this study, we prepared NO-releasing chitosan film (CS/NO film) and evaluated its anti-biofilm activity and in vivo wound healing efficacy against methicillin-resistant Staphylococcus aureus (MRSA) biofilm-infected wounds in diabetic mice. The in vitro release study showed sustained release of NO over 3 days in simulated wound fluid. The CS/NO film significantly enhanced antibacterial activity against MRSA by > 3 logs reduction in bacterial viability. Moreover, CS/NO film exhibited a 3-fold higher anti-biofilm activity than the control and CS film. In in vivo MRSA biofilm-infected wounds, the CS/NO film-treated group showed faster biofilm dispersal, wound size reduction, epithelialization rates, and collagen deposition than the untreated and CS film-treated groups. Therefore, the CS/NO film investigated in this study could be a promising approach for the treatment of MRSA biofilm-infected wounds.

Stabilizing Coacervate by Microfluidic Engulfment Induced by Controlled Interfacial Energy.

Low interfacial energy, an intrinsic property of complex coacervate, enables the complex coacervate to easily encapsulate desired cargo substances, making it widely used in encapsulation applications. Despite this advantage, the low interfacial energy of the complex coacervate makes it unstable against mechanical mixing, and changes in pH and salt concentration. Hence, a chemical cross-linker is usually added to enhance the stability of the complex coacervate at the expense of sacrificing all intrinsic properties of the coacervate, including phase transition of the coacervate from liquid to solid. In this study, we observed an abrupt increase in the interfacial energy of the coacervate phase in mineral oil. By controlling the interfacial energy of the coacervate phase using a microfluidic device, we successfully created double engulfed PEG-diacrylate (PEGDA) coacervate microparticles, named DEPOT, in which the coacervate is engulfed in a cross-linked PEGDA shell. The engulfed coacervate remained as a liquid phase, retained its original low interfacial energy property to encapsulate the desired cargo substances, and infiltrated into the target site by a simple solvent exchange from oil to water.

In Situ Hydrogel-Forming/Nitric Oxide-Releasing Wound Dressing for Enhanced Antibacterial Activity and Healing in Mice with Infected Wounds.

The eradication of bacteria from wound sites and promotion of healing are essential for treating infected wounds. Nitric oxide (NO) is desirable for these purposes due to its ability to accelerate wound healing and its broad-spectrum antibacterial effects. We developed an in situ hydrogel-forming/NO-releasing powder dressing (NO/GP), which is a powder during storage and forms a hydrogel when applied to wounds, as a novel NO-releasing formulation to treat infected wounds. An NO/GP fine powder (51.5 µm) was fabricated by blending and micronizing S-nitrosoglutathione (GSNO), alginate, pectin, and polyethylene glycol (PEG). NO/GP remained stable for more than four months when stored at 4 or 37 °C. When applied to wounds, NO/GP absorbed wound fluid and immediately converted to a hydrogel. Additionally, wound fluid triggered a NO release from NO/GP for more than 18 h. The rheological properties of hydrogel-transformed NO/GP indicated that NO/GP possesses similar adhesive properties to marketed products (Vaseline). NO/GP resulted in a 6-log reduction in colony forming units (CFUs) of methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, which are representative drug-resistant gram-positive and -negative bacteria, respectively. The promotion of wound healing by NO/GP was demonstrated in mice with full-thickness wounds challenged with MRSA and P. aeruginosa. Thus, NO/GP is a promising formulation for the treatment of infected wounds.

Transcriptomic Identification and Biochemical Characterization of HmpA, a Nitric Oxide Dioxygenase, Essential for Pathogenesis of Vibrio vulnificus.

Nitric oxide (NO) and its derivatives are important effectors of host innate immunity, disrupting cellular function of infecting pathogens. Transcriptome analysis of Vibrio vulnificus, an opportunistic human pathogen, identified a set of genes induced upon exposure to NO. Among them, VvhmpA (V. vulnificus hmpA), encoding a multidomain NO dioxygenase, was the most greatly induced upon exposure to NO and was thus further characterized. Absorption spectra demonstrated that VvHmpA is a heme protein in which the heme iron can exist in either reduced, NO-bound, or oxidized state. Biochemical studies revealed that VvHmpA is a flavohemoglobin containing equimolar amounts of heme and FAD as cofactors. The K M and k cat values of VvHmpA for NO at 37°C, the temperature encountered by V. vulnificus in the host, were greater than those at 30°C, indicating that VvHmpA detoxifies high levels of NO effectively during infection. Compared with the wild type, the VvhmpA mutant exhibited a lower NO-decomposition activity and impaired growth in the presence of NO in vitro. Also, the cytotoxicity and survival of the VvhmpA mutant infecting the NO-producing murine macrophage cells were lower than those of the wild type. Furthermore, the mouse lethality of the VvhmpA mutant was reduced compared to that of the parental wild type. The combined results revealed that VvHmpA is a potent virulence factor that is induced upon exposure to NO and important for the survival and pathogenesis of V. vulnificus during infection.

PEI/NONOates-doped PLGA nanoparticles for eradicating methicillin-resistant Staphylococcus aureus biofilm in diabetic wounds via binding to the biofilm matrix.

Wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilm represent a high risk in patients with diabetes. Nitric oxide (NO) has shown promise in dispersing biofilm and wound healing. For an effective treatment of MRSA biofilm-infected wounds, however, NO needs to be supplied to the biofilm matrix in a sustainable manner due to a short half-life and limited diffusion distance of NO. In this study, polyethylenimine/diazeniumdiolate (PEI/NONOate)-doped PLGA nanoparticles (PLGA-PEI/NO NPs) with an ability to bind to the biofilm matrix are developed to facilitate the NO delivery to MRSA biofilm-infected wound. In simulated wound fluid, PLGA-PEI/NO NPs show an extended NO release over 4 days. PLGA-PEI/NO NPs firmly bind to the MRSA biofilm matrix, resulting in a greatly enhanced anti-biofilm activity. Moreover, PLGA-PEI/NO NPs accelerate healing of MRSA biofilm-infected wounds in diabetic mice along with complete biofilm dispersal and reduced bacterial burden. These results suggest that the biofilm-binding NO-releasing NPs represent a promising NO delivery system for the treatments of biofilm-infected chronic wounds.

Bacteria-Targeted Clindamycin Loaded Polymeric Nanoparticles: Effect of Surface Charge on Nanoparticle Adhesion to MRSA, Antibacterial Activity, and Wound Healing.

Adhesion of nanoparticles (NPs) to the bacterial cell wall by modifying their physicochemical properties can improve the antibacterial activity of antibiotic. In this study, we prepared positively charged clindamycin-loaded poly (lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI) nanoparticles (Cly/PPNPs) and negatively charged clindamycin-loaded PLGA NPs (Cly/PNPs) and investigated the effect of NP adhesion to bacteria on the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The Cly/PPNPs and Cly/PNPs were characterized according to particle size, polydispersity index, surface charge, and drug loading. Both Cly/PPNPs and Cly/PNPs exhibited sustained drug release over 2 days. The Cly/PPNPs bind to the MRSA surface, thereby enhancing bactericidal efficacy against MRSA compared with the Cly/PNPs. Furthermore, compared with other groups, Cly/PPNPs significantly accelerated the healing and re-epithelialization of wounds in a mouse model of a MRSA-infected wounds. We also found that both NPs are harmless to healthy fibroblast cells. Therefore, our results suggest that the Cly/PPNPs developed in this study improve the efficacy of clindamycin for the treatment of MRSA-infected wounds.

Development of PLGA micro- and nanorods with high capacity of surface ligand conjugation for enhanced targeted delivery.

Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery. Targeting ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle surface. However, poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as PLGA. In this study, we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly (ethylene-alt-maleic acid) (PEMA). Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching method. The presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential measurements. Using the improved film-stretching method, the amount of protein conjugated to the surface of nanorods was increased three-fold. Transferrin-conjugated, nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified counterparts. Therefore, the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro- and nanoparticles with high capacity of surface modifications for enhanced targeted delivery.

S-Nitrosoglutathione loaded poly(lactic-co-glycolic acid) microparticles for prolonged nitric oxide release and enhanced healing of methicillin-resistant Staphylococcus aureus-infected wounds.

Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds have become a significant clinical issue worldwide. Recently, nitric oxide (NO) has emerged as a potent antibacterial agent against MRSA infections and a wound-healing enhancer. Nevertheless, clinical applications of NO have been largely restricted by its gaseous state and short half-life. In this study, our aim was to develop S-nitrosoglutathione (GSNO, an endogenous NO donor)-loaded poly(lactic-co-glycolic acid) [PLGA] microparticles (GSNO-MPs) that release NO over a prolonged period, to accelerate the healing of MRSA-infected wounds with less frequent dosing. GSNO was successfully encapsulated into PLGA microparticles by a solid-in-oil-in-water emulsion solvent evaporation method. Scanning electron microscopy and X-ray diffraction analyses confirmed the successful fabrication of GSNO-MPs. The latter released NO in a prolonged manner over 7 days and exerted a remarkable antibacterial activity against MRSA in a concentration- and time-dependent manner. Moreover, GSNO-MPs had good antibacterial efficacy and were found to accelerate wound healing in a mouse model of MRSA-infected wounds. Therefore, NO-releasing MPs devised in this study may be a promising option for the treatment of cutaneous wounds infected by drug-resistant bacteria such as MRSA.