Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance.

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

Engineering a hyaluronic acid-encapsulated tumor-targeted nanoplatform with sensitized chemotherapy and a photothermal effect for enhancing tumor therapy.

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.

H2S-Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation.

Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first-line treatments for IBD have limited efficacy and significant side effects. An innovative H2S-releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide-loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO-1, PI3K-AKT, and RAS/MAPK/AP-1, and inhibiting the p38/ERK MAPK, p65 NF-κB, and JAK-STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.

Tannic acid and zinc ion coordination of nanase for the treatment of inflammatory bowel disease by promoting mucosal repair and removing reactive oxygen and nitrogen species.

Colon mucosal overexpression of reactive oxygen and nitrogen species (RONS) accelerates the development of inflammatory bowel disease (IBD) and destroys the mucosa and its barrier. IBD can be alleviated by removing RONS from the inflamed colon. The preparation of strong and efficient nanoantioxidants remains a challenge despite the development of numerous nanoantioxidants. In this paper, Zn-TA nanoparticles with fine hollow microstructure (HZn-TA) were successfully prepared and could be effectively used to treat IBD. In the first step, ZIF-8 nanoparticles were synthesized by a one-pot method. On this basis, HZn-TA nanoparticles were etched by TA, and a multifunctional nanase was developed for the treatment of IBD. RONS, including reactive oxygen species (ROS) and nitric oxide (NO), can be eliminated to increase cell survival following Hydrogen peroxide (H2O2) stimulation, including reactive oxygen species (ROS) and nitric oxide (NO with hydrogen peroxide (H2O2). In a model for preventing and delaying acute colitis, clearance of RONS has been shown to reduce intestinal inflammation in mice by reducing colon damage, proinflammatory cytokine levels, the spleen index, and body weight. Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate zonula occludens protein 1 (ZO-1) and claudin-1 expression. Based on the results of this study, HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS. Therefore, we pioneered the application of HZn-TA nanoparticles for the treatment of IBD, which are capable of clearing RONS without significant adverse effects. STATEMENT OF SIGNIFICANCE: ➢ HZn-TA nanoparticles were successfully prepared and could be effectively used to treat IBD. ➢ Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate ZO-1 and claudin-1 expression. ➢ HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS.

Multifunctional Two-Dimensional Bi2Se3 nanodisks as a Non-Inflammatory photothermal agent for glioma treatment.

Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi2Se3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi2Se3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi2Se3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi2Se3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi2Se3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi2Se3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.

Multifunctional Cu2 Se/F127 Hydrogel with SOD-Like Enzyme Activity for Efficient Wound Healing.

Free radicals are secreted following skin damage and cause oxidative stress and inflammatory reactions that increase the difficulty of wound healing. In this study, copper-based nanozyme Cu2 Se nanosheets (NSs) are synthesized by an anion-exchange strategy and apply to wounds with F127 hydrogels to investigate the healing effect of this nanozyme composite hydrogels on wounds. Cu2 Se NSs have a large number of catalytically active centers, are simple to synthesize, require few reaction conditions and have a short synthesis cycle. In vitro experiments have shown that Cu2 Se NSs possess superoxide dismutase (SOD)-like activity and nitrogen radical scavenging activity and promote angiogenesis and fibroblast migration. The doping of Cu2 Se NSs into the F127 hydrogel does not have a significantly affect on the properties of the hydrogel. This hybridized hydrogel not only adapts to the irregular and complex morphology of acute wounds but also prolongs the duration of nanozyme action on the wound, thus promoting wound healing. Transcriptomic analysis further reveals the potential therapeutic mechanism of the Cu2 Se/F127 hydrogel in promoting acute wound healing. Animal experiments have shown that the Cu2 Se/F127 hydrogel has good biosafety. The Cu2 Se/F127 hydrogel provides an innovative idea for the development of hydrogel dressings for the treatment of acute wounds.

Application of nanotechnology in the treatment of glomerulonephritis: current status and future perspectives.

Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.

The progression of inorganic nanoparticles and natural products for inflammatory bowel disease.

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.

pH-responsive double-enzyme active metal-organic framework for promoting the healing of infected wounds.

The abuse of antibiotics accelerates the spread and evolution of drug-resistant bacteria, which seriously threatens human health. Hydroxyl radicals (•OH) are generated by peroxidase in the presence of H2O2, which is strongly oxidizing and can effectively kill bacteria. However, high production costs and poor stability limit the clinical use of natural enzymes. "Nanozyme" is a general term for nanomaterials with catalytic activity similar to that of biological enzymes. Compared to biological enzymes, nanozymes have the advantages of low cost, facile preparation, and easy storage, making them a good choice for the development of antibacterial agents. Here, a nickel-based metal-organic framework (Ni-MOF) with dual enzymatic activity that switches depending on the pH environment was studied. In a slightly acidic environment, Ni-MOF can react with hydrogen peroxide to produce hydroxyl radicals that kill bacteria; in a neutral environment, Ni-MOF instead removes excessive reactive oxygen species (ROS) and promotes the transformation of macrophages into M2 macrophages. Compared to most nanozymes, Ni-MOF has unique electrical conductivity and better biosafety. The results of animal experiments show that Ni-MOF can not only treat infected wounds but also promote the healing of acute wounds and exhibits great clinical application potential.

Copper Nanodots-Based Hybrid Hydrogels with Multiple Enzyme Activities for Acute and Infected Wound Repair.

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.

Unraveling the mechanism of Yiqi Jiedu formula against nasopharyngeal carcinoma: An investigation integrating network pharmacology, serum pharmacochemistry, and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Jiedu formula (YQJDF), rooted in the traditional Chinese medicinal principle of "tonifying qi and detoxifying", is remarkably efficacious in the clinical treatment of nasopharyngeal carcinoma (NPC). Previous studies have shed light on some of its anti-NPC effects and mechanisms, but the responsible pharmacological substances and their precise mechanisms of action remain unclear. AIM OF THE STUDY: The purpose of this study was to identify components of YQJDF that entered the bloodstream and to investigate their mechanisms of action against NPC through network pharmacology and serum metabolomics. MATERIAL AND METHODS: Components of YQJDF in serum were identified using liquid chromatography-tandem mass spectrometry. With these serum species as the focus of our research, network pharmacology analysis was used to identify active compounds and target genes that might mediate the efficacy of YQJDF in the treatment of NPC. Following establishment of an NPC xenograft model in nude mice, a non-targeted metabolomics approach was adopted to identify significant serum metabolites and metabolic pathways influenced by YQJDF. RESULTS: Thirty-six components of YQJDF were identified, primarily consisting of alkaloids, phenylpropanoids, and flavonoids. Notably, pathways such as PI3K/AKT, factors associated with Epstein-Barr virus infection, IL-17 signaling, and lipid metabolism, were highlighted as potential therapeutic targets of YQJDF during NPC treatment. Additionally, our findings suggested that YQJDF modified the metabolism of arginine and proline in the serum of mice bearing nasopharyngeal tumor grafts. CONCLUSIONS: This study identified the primary active components of YQJDF, highlighting its holistic role in the treatment of NPC through multiple targets and pathways. Furthermore, our findings provided a roadmap for future research into the mechanism of YQJDF in the therapy of NPC, setting the stage for its clinical application.

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis.

BACKGROUND: EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects. METHODS: We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe3+ to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation. RESULTS: Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased H2O2 release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities. CONCLUSION: This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment.

Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy.

Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity. Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer. HfC NPs possessed satisfactory near-infrared (NIR) absorption, good photothermal conversion efficiency (PTCE, 36.8 %) and photothermal stability. Furthermore, holding large surface areas and intrinsic redox-active sites, HfC NPs exhibited excellent anti-inflammatory properties due to their antioxidant and superoxide dismutase (SOD) enzymatic activities. In vitro and in vivo experiments confirmed that HfC NPs converted light energy into heat energy upon NIR laser irradiation to kill cancer cells through PTT and achieved a better therapeutic effect by anti-inflammatory effects after PTT. This work highlights that multifunctional HfC NPs can be applied in noninflammatory PTT with outstanding safety and efficacy.

[Biosynthesis of immunosuppressant tacrolimus: a review].

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.

A multifunctional cascade nanoreactor based on Fe-driven carbon nanozymes for synergistic photothermal/chemodynamic antibacterial therapy.

Healing bacterial chronic wounds caused by hyperglycemia is of great significance to protect the physical and mental health of diabetic patients. In this context, emerging chemodynamic therapy (CDT) and photothermal therapy (PTT) with broad antibacterial spectra and high spatiotemporal controllability have flourished. However, CDT was challenged by the near-neutral pH and inadequate H2O2 surrounding the chronic wound site, while PTT showed overheating-triggered side effects (e.g., damaging the normal tissue) and poor effects on thermotolerant bacterial biofilms. Therefore, we engineered an all-in-one glucose-responsive photothermal nanozyme, GOX/MPDA/Fe@CDs, consisting of glucose oxidase (GOX), Fe-doped carbon dots (Fe@CDs), and mesoporous polydopamine (MPDA), to efficiently treat chronic diabetic wound bacterial infections and eradicate biofilms without impacting the surrounding normal tissues. Specifically, GOX/MPDA/Fe@CDs produced a local temperature (∼ 45.0°C) to enhance the permeability of the pathogenic bacterium and its biofilm upon near-infrared (NIR) 808 nm laser irradiation, which was seized to initiate endogenous high blood glucose to activate the catalytic activity of GOX on the GOX/MPDA/Fe@CD surface to achieve the simultaneous self-supplying of H2O2 and H+, cascade catalyzing •OH production via a subsequent peroxidase-mimetic activity-induced Fenton/Fenton-like reaction. As such, the in vivo diabetic wound infected with methicillin-resistant Staphylococcus aureus was effectively healed after 12.0 days of treatment. This work was expected to provide an innovative approach to the clinical treatment of bacterially infected diabetic chronic wounds. STATEMENT OF SIGNIFICANCE: An all-in-one glucose-responsive photothermal nanozyme GOX/MPDA/Fe@CDs was constructed. Cascade nanozyme GOX/MPDA/Fe@CDs self-supply H2O2 and H+ to break H2O2 and pH limits to fight bacterial infections. Synergistic chemotherapy and photothermal therapy with nanozyme GOX/MPDA/Fe@CDs accelerates healing of biofilm-infected diabetic wounds.

Two-dimensional TiO nanosheets with photothermal effects for wound sterilization.

To combat multidrug-resistant bacteria, researchers have poured into the development and design of antimicrobial agents. Here, low-cost two-dimensional (2D) antibacterial material titanium monoxide nanosheets (TiO NSs) were prepared by an ultrasonic-assisted liquid-phase exfoliation method. When cultured with bacteria, TiO NSs showed intrinsic antimicrobial capacity, possibly due to membrane damage caused by the sharp edges of TiO NSs. Under near-infrared (NIR) laser irradiation, TiO NSs showed high photothermal conversion efficiency (PTCE) and sterilization efficiency. By combining these two antibacterial mechanisms, TiO NSs exhibited a strong killing effect on Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Especially after treatment with TiO NSs (150 µg mL-1) +near-infrared (NIR) light irradiation, both bacteria were completely killed. In vivo experiments on wound repair of bacterial infection further confirmed its antibacterial effect. In addition, TiO NSs had no obvious toxicity or side effects, so as a kind of broad-spectrum 2D antibacterial nanoagent, TiO NSs have broad application prospects in the field of pathogen infection.

Injectable Hydrogel Containing TiO Nanosheets for Synergistic Photothermal/Thermodynamic Therapy.

Tumors have become the biggest obstacle to human health, and there are various treatment methods at present. Photothermal therapy (PTT) is usually ineffective and does not inhibit tumor progression due to the inability of the lasers to penetrate deeply. Therefore, most existing studies chose a 1064 nm laser with stronger penetrating power; meanwhile, studies have shown that the inclusion of harmful free radicals can significantly improve the antitumor efficacy. Herein, TiO nanosheets (NSs) were creatively prepared and encapsulated with an alkyl radical generator {2,2'-azobis[2-(2-imidazoline-2-yl)propane] dihydrochloride, [AIPH]} in sodium alginate (ALG) hydrogel for effective tumor killing by PTT and pairing with dangerous free radicals. TiO NSs were obtained by the liquid-phase exfoliation method, together with AIPH, which were in situ coencapsulated multifunctional hydrogels formed by the combination of Ca2+ and ALG. This ALG hydrogel could enrich TiO NSs and AIPH at the tumor site for a long time, and through the excellent photothermal properties of TiO NSs, AIPH could slowly and effectively generate alkyl radicals at the tumor site, which, in turn, gave it a better antitumor effect compared with that of TiO NSs in the deep hypoxic environment of the tumor. The AIPH + TiO + ALG hydrogel has distinctive anticancer capabilities based on the results of both in vivo and in vitro experiments. This material also has good biosafety. By combining PTT and free radical treatment, this work provides a novel therapeutic method to achieve oxygen-independent free radical production and enhance therapeutic efficacy.

Molecular Engineering Design of Enhanced Donor-Acceptor Therapeutic Reagent for Efficient Image-Guided Photodynamic Therapy.

The greatest barrier to the further development and clinical application of tumor image-guided photodynamic therapy (PDT), is the inconsistency between the fluorescence intensity and singlet oxygen generation yield of the photosensitizer under light excitation. Herein, a novel donor-acceptor (D-A) system is designed from the point of molecular selection by wrapping a classical porphyrin molecule (5,10,15,20-tetraphenylphorphyrin, H2 TPP) as an acceptor into conjugated polymer (Poly[N,N'-bis(4-butylpheny)-N,N'-bis(phenyl)benzidine], ADS254BE) as a donor through fluorescence resonance energy transfer (FRET) mechanism, which exhibits bright red emission centered at 650 nm (quantum yield, 0.12), relatively large Stoke shift of 276 nm, enhanced singlet oxygen generation rate of 0.73, and excellent photostability. The investigations on distribution and killing effect of nanomaterials in cancer cells reveal that ADS254BE/H2 TPP NPs can accumulate in the cytoplasm for imaging while simultaneously producing a large amount of singlet oxygen to remarkably kill cancer cells, which can be used for real-time image-guided PDT. In the xenograft tumor model, real-time imaging and long-term tracing in tumor tissue with ADS254BE/H2 TPP NPs disclose that the growth of lung cancer in mice can be effectively inhibited during in situ imaging. From the standpoint of molecular engineering design, this work provides a feasible strategy for novel D-A systems to improve the development of image-guided PDT.