Future embracing: exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy.

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and is associated with high rates of end-stage renal disease. Early detection and precise interventions are crucial for improving patient prognosis and quality of life. However, the current diagnosis primarily relies on renal biopsies and traditional biomarkers, which have limitations. Additionally, targeted therapeutic strategies are lacking. Exosomes, small vesicles that facilitate intercellular communication, have emerged as potential noninvasive diagnostic markers due to their stability, diverse cargo, and rapid detectability. They also hold promise as carriers for gene and drug delivery, presenting innovative opportunities in renal disease prognosis and treatment. However, research on exosomes in the context of idiopathic membranous nephropathy (IMN) remains limited, with a focus on exploring urinary exosomes as IMN markers. In this review, we summarize the current status of MN diagnosis and treatment, highlight the fundamental characteristics of exosomes, and discuss recent advancements in their application to IMN diagnosis and therapy. We provide insights into the clinical prospects of exosomes in IMN and acknowledge potential challenges. This article aims to offer forward-looking insights into the future of exosome-mediated IMN diagnosis and treatment, indicating a revolutionary transformation in this field.

Catalase-positive Staphylococcus epidermidis based cryo-millineedle platform facilitates the photo-immunotherapy against colorectal cancer via hypoxia improvement.

The synergistic anti-tumor impact of phototherapy and a cascading immune response are profoundly limited by hypoxia and a weakened immune response. Intravenous and intratumoral injection of therapeutic drugs also cause pain, rapid drug clearance and low utilization rates. Here, a novel cryo-millineedle platform for intratumoral delivery of a phototherapy system, S.epi@IR820, is developed in this work, combining the properties of Staphylococcus epidermidis (S. epidermidis) and IR820 for photo-immunotherapy of colorectal cancer. In this cryo-millineedle platform, S. epidermidis enhances the near-infrared absorption and light stability of IR820 and catalyzes the decomposition of H2O2 into O2 via an endogenous catalase to relieve tumor hypoxia, improve phototherapy and enhance immunogenic cell death (ICD). More interestingly, the native immunogenicity of S. epidermidis and ICD elicited by phototherapy achieved a potent anti-tumor immune response. To the best of our knowledge, this is the first study to utilize native S. epidermidis to relieve hypoxia and facilitate phototherapy. Both in vitro and in vivo experiments showed that the millineedle based phototherapy system can efficiently catalyse the decomposition of H2O2 into O2, facilitate phototherapeutic killing of CT26 tumor cells by S.epi@IR820 and enhance ICD, thus successfully activated the immune response and achieved the photo-immunotherapy against colorectal cancer. In conclusion, this study provides a novel strategy for enhanced anti-tumor efficiency of photo-immunotherapy, and develops an effective method for orthotopic administration of tumors.

Application of metal-organic frameworks in infectious wound healing.

Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.

Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis.

Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood-retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

Characterization and the first complete genome sequence of a novel strain of Bergeyella porcorum isolated from pigs in China.

BACKGROUND: Bergeyella porcorum is a newly identified bacterium that has an ambiguous relationship with pneumonia in pigs. However, few studies have adequately characterized this species. RESULTS: In this study, we analyzed the morphological, physiological, and genomic characteristics of the newly identified B. porcorum sp. nov. strain QD2021 isolated from pigs. The complete genome sequence of the B. porcorum QD2021 strain consists of a single circular chromosome (2,271,736 bp, 38.51% G + C content), which encodes 2,578 genes. One plasmid with a size of 70,040 bp was detected. A total of 121 scattered repeat sequences, 319 tandem repeat sequences, 4 genomic islands, 5 prophages, 3 CRISPR sequences, and 51 ncRNAs were predicted. The coding genes of the B. porcorum genome were successfully annotated across eight databases (NR, GO, KEGG, COG, TCDB, Pfam, Swiss-Prot and CAZy) and four pathogenicity-related databases (PHI, CARD, VFDB and ARDB). In addition, a comparative genome analysis was performed to explore the evolutionary relationships of B. porcorum QD2021. CONCLUSIONS: To our knowledge, this is the first study to provide fundamental phenotypic and whole-genome sequences for B. porcorum. Our results extensively expand the current knowledge and could serve as a valuable genomic resource for future research on B. porcorum.

Advances in nanomaterial-targeted treatment of acute lung injury after burns.

Acute lung injury (ALI) is a common complication in patients with severe burns and has a complex pathogenesis and high morbidity and mortality rates. A variety of drugs have been identified in the clinic for the treatment of ALI, but they have toxic side effects caused by easy degradation in the body and distribution throughout the body. In recent years, as the understanding of the mechanism underlying ALI has improved, scholars have developed a variety of new nanomaterials that can be safely and effectively targeted for the treatment of ALI. Most of these methods involve nanomaterials such as lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles and other nanomaterials, which are targeted to reach lung tissues to perform their functions through active targeting or passive targeting, a process that involves a variety of cells or organelles. In this review, first, the mechanisms and pathophysiological features of ALI occurrence after burn injury are reviewed, potential therapeutic targets for ALI are summarized, existing nanomaterials for the targeted treatment of ALI are classified, and possible problems and challenges of nanomaterials in the targeted treatment of ALI are discussed to provide a reference for the development of nanomaterials for the targeted treatment of ALI.

In situ hydrogel based on Cu-Fe3O4 nanoclusters exploits oxidative stress and the ferroptosis/cuproptosis pathway for chemodynamic therapy.

Chemodynamic therapy (CDT) involving the use of metal nanozymes presents new opportunities for the treatment of deep-seated tumors. However, the lower ROS catalytic rate and dependence on high H2O2 concentrations affect therapeutic efficacy. To address this issue, a hydrogel was constructed for the treatment of osteosarcoma by combining Cu-Fe3O4 nanozymes (NCs) and artemisinin (AS) coencapsulated in situ with sodium alginate (ALG) and calcium ions. This hydrogel can release nanoparticles and AS within tumor tissue for an extended period of time, utilizing the multienzyme activity of NCs to achieve ROS accumulation. The carbon radicals (•C) generated from the interaction of Fe2+/Cu2+ with AS amplify oxidative stress, leading to tumor cell damage. Simultaneously, the NCs activate ferroptosis via the GPX4 pathway by depleting GSH and activate cuproptosis via the DLAT pathway by causing intracellular copper overload, enhancing therapeutic efficacy. In vitro experiments confirmed that the NCs-AS-ALG hydrogel has an excellent tumor cell killing effect, while in vivo experimental results demonstrated that it can effectively eliminate tumors with excellent biocompatibility, providing a new approach for osteosarcoma treatment.

Sprayable, thermosensitive hydrogels for promoting wound healing based on hollow, porous and pH-sensitive ZnO microspheres.

A solvothermal method and the subsequent heat treatment process were developed to fabricate hollow ZnO particles with hierarchical pores on a large scale. The as-obtained hollow, porous ZnO microspheres with tunable sizes, high specific surface areas, pH sensitivity, antibacterial properties, and high adsorption capacities showed significant advantages for drug delivery. Sprayable hydrogels containing hollow, porous ZnO microspheres and curcumin nanoparticles (CNPs) were prepared to accelerate wound healing. The water-dispersed CNPs promoted both the migration of fibroblasts and angiogenesis and an aqueous solution of Pluronic F127 (a temperature-sensitive phase-change hydrogel material) was shown to be an effective choice for medical dressings. The experimental data suggest that hollow, porous ZnO microspheres can be loaded with additional CNPs to achieve continuous long-term therapeutic effects.

Multifunctional Adaptable Injectable TiN-Based Hydrogels for Antitumor and Antidrug-Resistant Bacterial Therapy.

The close relationship between bacteria and tumors has recently attracted increasing attention, and an increasing number of resources are being invested in the research and development of biomedical materials designed for the treatment of both. In this study, prefabricated TiN nanodots (NDs) and Fe(CO)5 nanoparticles are combined into sodium alginate (ALG) hydrogels to create a biomedical material for the topical treatment of breast cancer and subcutaneous abscesses, and a pseudocatalytic hydrogel with intrinsic photothermal and antibacterial activities is synthesized. TiN+Fe(CO)5+ALG hydrogels are used to determine the ability of Fe(CO)5 to promote CO production. Moreover, TiN NDs catalyze the production of reactive oxygen species (ROS) from hydrogen peroxide in tumor microenvironments and exhibit excellent photothermal conversion properties. After local injection of the TiN+Fe(CO)5+ALG hydrogel into subcutaneous tumors and subcutaneous abscesses, and two-zone near-infrared (NIR-II) irradiation, tumor cells and methicillin-resistant Staphylococcus aureus are effectively removed by the hydrogel, the mouse epidermis exhibiting complete recovery within 8 d, indicating that this hydrogel exhibits better antibacterial efficacy than the small-molecule antibiotic penicillin. This study demonstrates the potential of novel hydrogels for antitumor and antimicrobial combination therapy and aims to provide design ideas for the research and development of multifunctional antitumor and antimicrobial drug combinations.

CuCo2O4 Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death.

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCo2O4 exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O2•-. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCo2O4 was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCo2O4 was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCo2O4 on biofilms formed by bacteria. In vivo, CuCo2O4 significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu2+ overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.

Accelerated Screening of Alternative DNA Base-Organic Molecule-Base Architectures via Integrated Theory and Experiment.

Organic molecule-mediated noncanonical DNA self-assembly expands the standard DNA base-pairing alphabets. However, only a very limited number of small molecules have been recognized as mediators because of the tedious and complicated experiments like crystallization and microscopy imaging. Here we present an integrative screening protocol incorporating molecular dynamics (MD) for fast theoretical simulation and native polyacrylamide gel electrophoresis for convenient experimental validation. Melamine, the molecule that was confirmed mediating noncanonical DNA base-pairing, and 38 other candidate molecules were applied to demonstrate the feasibility of this protocol. We successfully identified seven stable noncanonical DNA duplex structures, and another eight novel structures with sub-stability. In addition, we discovered that hairpins at both ends can significantly stabilize the noncanonical DNA structures, providing a guideline to design small organic molecule-incorporated DNA structures. Such an efficient screening protocol will accelerate the design of alternative DNA-molecule architectures beyond Watson-Crick pairs. Considering the wide range of potential mediators, it will also facilitate applications such as noncovalent, highly dense loading of drug molecules in DNA-based delivery system and probe design for sensitive detection of certain molecules.

W-GA nanodots restore intestinal barrier functions by regulating flora disturbance and relieving excessive oxidative stress to alleviate colitis.

Inflammatory bowel disease (IBD) may arise due to disruption of mucosal barriers as a result of dysregulation of the intestinal flora and excessive oxidative stress. The creation of nanomaterials with only microbiota-regulating effects often leads to inadequate therapeutic outcomes caused by the disruption of a healthy microbial balance and the emergence of tissue harm caused by excessive oxidative stress. This report describes the multifunctional activity of ultrasmall W-GA nanodots, which can precisely regulate the intestinal microbiome by inhibiting the abnormal expansion of Enterobacteriaceae during colitis and alleviating the damage caused by oxidative stress to the reconstructive microflora, ultimately restoring intestinal barrier function. W-GA nanodots have been synthesized through a simple coordination reaction and can be dispersed in various solvents in vitro, demonstrating favorable safety profiles in cells, significant clearance of reactive oxygen and nitrogen species (RONS), and increased cell survival in models of oxidative stress induced by hydrogen peroxide (H2O2). Through oral or intravenous administration, the W-GA nanodots were shown to be highly safe when tested in vivo, and they effectively reduced colon damage in mice with DSS-induced colitis by restoring the integrity of the intestinal barrier. W-GA nanodots have enabled the integration of microflora reprogramming and RONS clearance, creating a potent therapeutic strategy for treating gut inflammation. Consequently, the development of W-GA nanodots represents a promising strategy for enhancing the formation and preservation of the intestinal barrier to treat IBD by suppressing the growth of Enterobacteriaceae, a type of facultative anaerobic bacterium, and facilitating the effective removal of RONS. Ultimately, this leads to the restoration of the intestinal barrier's functionality. STATEMENT OF SIGNIFICANCE: An increasing number of nanoparticles are under development for treating inflammatory bowel disease. Although they can alleviate inflammation symptoms by regulating reactive oxygen and nitrogen species (RONS) and microbiota, their understanding of the mechanism behind microbiota regulation is limited. This study synthesized W-GA nanodots using a straightforward one-pot synthesis method. Simple synthesis holds significant promise for clinical applications, as it encompasses multiple nanoenzyme functions and also exhibits Enterobacteriaceae inhibitory properties.Thus, it contributes to ameliorating the current medical landscape of inflammatory bowel disease.

Nanozyme-Incorporated Microneedles for the Treatment of Chronic Wounds.

Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti-inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research.

Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria.

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at the wound site triggers the production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins and cells. This can lead to chronic wounds, posing severe risks. Therefore, eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing. Nanozymes, possessing enzyme-like catalytic activity, can convert endogenous substances into highly toxic substances, such as ROS, to combat bacteria and biofilms without inducing drug resistance. However, the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy. Thus, developing nanozymes with multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) with diverse enzymatic activities to aid wound healing and combat bacterial infections. Under acidic conditions, due to their glutathione (GSH) depletion and peroxidase (POD)-like activity, Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects. However, in a neutral environment, the Ru-PC NPs, with catalase (CAT) activity, decompose H2O2 to O2, alleviating hypoxia and ensuring a sufficient oxygen supply. Furthermore, Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase (SOD) enzyme activity, effectively scavenging excess ROS and reactive nitrogen species (RNS) in a neutral environment. This maintains the balance of the antioxidant system and prevents inflammation. Ru-PC NPs also promote the polarization of macrophages from M1 to M2, facilitating wound healing. More importantly, Ru-PC NPs show good biosafety with negligible toxicity. In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing. The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.

Exosomes derived from mesenchymal stem cells containing berberine for ulcerative colitis therapy.

Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber.

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.

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.

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.

Multifunctional Cu2Se/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 Cu2Se 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. Cu2Se 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 Cu2Se NSs possess superoxide dismutase (SOD)-like activity and nitrogen radical scavenging activity and promote angiogenesis and fibroblast migration. The doping of Cu2Se 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 Cu2Se/F127 hydrogel in promoting acute wound healing. Animal experiments have shown that the Cu2Se/F127 hydrogel has good biosafety. The Cu2Se/F127 hydrogel provides an innovative idea for the development of hydrogel dressings for the treatment of acute wounds.