Photothermal therapy (PTT) has come into view as an innovative strategy for colorectal cancer (CRC) therapy based on its exceptional spatial selectivity and minimal side effects. However, clinical PTT is severely restricted due to the limited depth of laser penetration and the self-protective nature of cells with heat shock protein (HSP) upregulation. Herein, we prepared a synergistic PTT/ST near-infrared (NIR) nanoplatform (PR NPs), which is self-assembled from the NIR phototherapeutic agent PPAB and the glucose transporter 1 (GLUT1) inhibitor resveratrol (RES) to fight CRC. The PR NPs display enhanced cancer PTT efficiency owing to the downregulation of adenosine triphosphate (ATP)-dependent HSPs mediated by RES. Meanwhile, the enhanced metabolism and energy consumption triggered by PTT further exacerbate the energy crisis, amplifying the starvation therapy (ST) effect. More significantly, the RES released from PR NPs can also specifically target GLUT1 in CRC cells to promote apoptosis and suppress migration. Hence, the versatile NIR PR NPs can simultaneously enable efficient photothermal ablation and precise energy deprivation to improve antitumor outcome, providing a novel paradigm for CRC treatment.
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Open Access
Research Article
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Effectively controlling bacterial infections and reducing oxidative stress and inflammatory reactions are important steps in wound healing. However, owing to the improper use of antibiotics and inadequate control of infections in recent years, the emergence of many broad-spectrum drug-resistant strains has exacerbated the threat of infected wounds to human health. Recent studies have shown that bimetallic nanozymes may become an effective means of treating drug-resistant bacterial infections because of their unique physical properties and excellent antibacterial properties. In this study, silver iron bimetallic nanozymes with multiple enzyme activities (peroxidase, glutathione peroxidase, and superoxide dismutase) were successfully synthesized for the treatment of skin wounds. Notably, the prepared Vo-AgFeO2–x exhibited different enzyme activities under different pH conditions. In acidic environments, Vo-AgFeO2–x can catalyze H2O2 to generate reactive oxygen species (ROS), deplete glutathione (GSH), and kill bacteria. In a neutral environment, Vo-AgFeO2−x can eliminate free radicals, control inflammatory reactions, and accelerate wound healing. In vivo experiments have shown that Vo-AgFeO2−x can promote the healing of infected wounds and has good biological safety. These findings suggest that it can be used as a safe and efficient antibacterial drug to achieve effective treatment of bacterial infection-induced wounds.
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Review Article
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Bacterial infections pose a serious threat to public health, causing millions of deaths annually. Antibiotic therapy remains the primary treatment; however, its overuse has led to the emergence of multidrug-resistant superbugs, which endanger both public health and the environment. Inspired by natural enzymes, researchers have developed nanozymes. These novel agents possess catalytic properties similar to those of natural enzymes and offer advantages such as low cost, high stability, durability, and adjustable size. These characteristics make nanozymes a promising approach for combating bacterial infections, particularly in addressing the challenges posed by antibiotic resistance. This review provides a comprehensive overview of recent advances in biomimetic nanozymes for antibacterial applications, focusing on their functional and structural biomimicry, as well as biomimetic modifications aimed at enhancing biocompatibility, and highlights future perspectives on their application in treating bacterial infections.
Open Access
Review Article
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Cancer remains a formidable global public health burden, with an estimated 2.0 million incident cases and 618,000 deaths anticipated in 2025. Despite the broad clinical deployment of surgery, radiotherapy, chemotherapy and immunotherapy, tumor remains plagued by recurrence and metastasis. Nanozymes, emerging as potent tools in oncology, mimic natural enzymes with high catalytic stability and can synergize with photothermal therapy, photodynamic therapy, chemodynamic therapy, and other modalities to effectively eradicate tumors. This review focuses on nanozyme-based immunotherapy and proposes a novel "closed-loop regulatory" strategy. By leveraging the multi-enzyme activities and stimuli-responsiveness of nanozymes, dynamically senses the tumor microenvironment for recognition, implements catalytic interventions, and establishes self-amplifying feedback loops via immune activation or metabolic remodeling. This closed-loop system eliminates immunosuppressive signals while enhancing pro-immunity, thereby overcoming the limitations of linear therapies and enabling sustained efficacy amplification. Despite its promise, challenges including long-term biosafety, targeted delivery, and manufacturing scalability require further resolution.
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A large number of apoptotic vesicles (ApoVs) are released during apoptosis, and mesenchymal stem cells (MSCs)-derived ApoVs (MSC-ApoVs) have significant efficacy in the field of tissue regeneration. ApoVs extracted by density gradient centrifugation have a larger volume and wider diameter distribution, high yield and drug loading efficiency, and inherit the apoptotic traces of FasL, phosphatidylserine (PS), ICAM-3, and other parent cells and the ability to target cell membranes. MSC-ApoVs can significantly promote skin wound healing; however, whether they can promote wound healing in the early stages by playing an antibacterial role is unclear. In the present study, human umbilical cord MSC-derived ApoVs (hucMSC-ApoVs) were extracted and prepared. An in vitro antibacterial test confirmed that hucMSC-ApoVs effectively inhibited the growth of bacteria and sterilized bacteria. In vivo experiments revealed that hucMSC-ApoVs can accelerate the healing of infected wounds. Further exploration of the antibacterial mechanism revealed that hucMSC-ApoVs significantly interfered with bacterial catabolic processes. In gram-positive bacteria (MRSA), hucMSC-ApoVs affect the normal metabolic process of bacteria mainly by inhibiting the metabolism of purines, pyrimidines, and other nucleotides of MRSA and arginine biosynthesis, whereas in the gram-negative bacteria E. coli, they affect this process. HucMSC-ApoVs inhibit bacterial metabolic processes such as sulfur, fatty acid, arginine, and proline metabolism; in particular, hucMSC-ApoVs can interfere with the ethanolamine metabolic process in E.coli by regulating a series of ethanolamine genes (Eut) that encode ethanolamine degrading enzymes. These findings suggest that hucMSC-ApoVs are useful natural reagents for inhibiting wound bacterial infection and promoting wound healing.
The therapeutic efficiency of sonodynamic therapy (SDT) mainly depends on the presence of oxygen (O2) to generate harmful reactive oxygen species (ROS); thus, the hypoxic tumor microenvironment significantly limits the efficacy of SDT. Therefore, the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT. In this study, a biomimetic drug delivery system (C-TiO2/AIPH@PM) composed of an alkyl-radical generator (2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH)-loaded C-TiO2 hollow nanoshells (HNSs) as the inner cores, and a platelet membrane (PM) as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy. The PM encapsulation can significantly prolong the blood circulation time of C-TiO2/AIPH@PM compared with C-TiO2/AIPH while enabling C-TiO2/AIPH@PM to achieve tumor targeting. C-TiO2/AIPH@PM can efficiently produce ROS and alkyl radicals, which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions. Furthermore, the generation of these radicals improves the efficiency of SDT. In addition, nitrogen (N2) produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold, thereby enhancing the penetration of C-TiO2/AIPH@PM at the tumor sites. Both in vitro and in vivo experiments demonstrate that C-TiO2/AIPH@PM possesses good biosafety, ultrasound imaging performance, and excellent anticancer efficacy. This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.
Single-atom nanozymes (SAZs) with peroxidase (POD)-like activity have good nanocatalytic tumor therapy (NCT) capabilities. However, insufficient hydrogen peroxide (H2O2) and hydrogen ions in the cells limit their therapeutic effects. Herein, to overcome these limitations, a biomimetic single-atom nanozyme system was developed for self-enhanced NCT. We used a previously described approach to produce platelet membrane vesicles. Using a high-temperature carbonization approach, copper SAZs with excellent POD-like activity were successfully synthesized. Finally, through physical extrusion, a proton pump inhibitor (PPI; pantoprazole sodium) and the SAZs were combined with platelet membrane vesicles to create PPS. Both in vivo and in vitro, PPS displayed good tumor-targeting and accumulation abilities. PPIs were able to simultaneously regulate the hydrogen ion, glutathione (GSH), and H2O2 content in tumor cells, significantly improve the catalytic ability of SAZs, and achieve self-enhanced NCT. Our in vivo studies showed that PPS had a tumor suppression rate of > 90%. PPS also limited the synthesis of GSH in cells at the source; thus, glutamine metabolism therapy and NCT were integrated into an innovative method, which provides a novel strategy for multimodal tumor therapy.
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