Recently, reactive oxygen species (ROS)-independent mimetics of oxidase with Au nanoclusters (NCs) as the catalysts and MnO₂ as electron acceptor have gained attention. In this study, we aim to explore the oxidase-mimicking potential of bovine serum albumin (BSA)-templated metal nanoclusters (BSA-M NCs, where M = Ag, Pt, Cu, or Cd) beyond Au NCs in boosting the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by MnO₂, denoted as BM@Metal. The oxidase-mimetic activity of BM@Metal is independent of ROS and generally enhanced by the incorporation of metal nanoclusters. Notably, this enhancement varies with the metal species, with BSA-Cd exhibiting the highest activity. The X-ray photoelectron spectroscopy (XPS) analysis confirms mixed valence states (Mn(IV)/Mn(II)) in BM@Cd. Given that the catalytic activity is closely linked to the substrate adsorption, the label-free isothermal titration calorimetry was employed to probe the affinity between TMB and BSA-M NCs, which provides a robust approach for probing the interface adsorption. The results reveal that the superior catalytic performance of BSA-Cd correlates with enhanced TMB adsorption, likely facilitated by coordination and hydrophobic interactions. Finally, the superior catalytic performance of BSA-M NCs on the oxidation of TMB by MnO₂ has inspired us to fabricate the assay for analyzing α-glucosidase’s activity. This work not only demonstrates the versatility of metal NCs in constructing ROS-independent oxidase mimetics but also provides interfacial adsorption engineered strategy for the rational design of superior ROS independent mimetics of natural oxidase.

Tumor microenvironment-responsive nanocatalysts enhance reactive oxygen species (ROS) accumulation by compromising tumor antioxidant defenses, offering a promising cancer treatment strategy. Leveraging the catalytic potential of metal-phenolic networks (MPNs), this study constructed GA-Cu MPNs as multifunctional carriers. Since endogenous catalase (CAT) limits hydrogen peroxide (H₂O₂) accumulation, the CAT inhibitor 3-amino-1,2,4-triazole was encapsulated within the MPNs to form GA-Cu-AT, which was further modified with hyaluronic acid to produce GA-Cu-AT@HA. GA-Cu-AT@HA converts superoxide anions to H₂O₂, which is further transformed into toxic hydroxyl radicals through peroxidase-like activity, while inhibits endogenous CAT to amplify oxidative stress. Under 808 nm near-infrared light, it exhibits photothermal activity, enabling synergistic photothermal-catalytic effects. In vitro, it induces ROS accumulation, mitochondrial damage, apoptosis, and immunogenic cell death (ICD). In in situ hepatocellular carcinoma, GA-Cu-AT@HA effectively suppresses tumor growth, induces apoptosis, and enhances damage-associated molecular patterns release via targeted accumulation. In 4T1 breast cancer xenografts, photothermal therapy enhances the infiltration of CD8⁺ T cells into tumors, promotes dendritic cell maturation, and elicits systemic CD8⁺ T cell responses, and reduces regulatory T cells. This tripartite strategy, encompassing oxidative cytotoxicity, ICD activation, and immune microenvironment remodeling, offers a novel approach for tumor redox regulation therapy.

Chimeric antigen receptor T-cells (CAR-T) therapy has demonstrated significant anti-tumor responses in hematological malignancies and even solid tumors. However, the overactivation of CAR-T cells in vivo can lead to cytokine release syndrome (CRS), with the unpredictable timing and severity of its onset making it difficult to manage effectively. In this study, a strategy was proposed to prevent and treat CAR-T cell-induced CRS in situ by conjugating T cell receptor (TCR)-signaling-responsive siltuximab nanogels (NGs) with CAR-T cells. These siltuximab NGs, formed via NHS-S-S-NHS cross-linking, non-covalently bind to CAR-T cells through anti-CD45, significantly prolonging NGs retention time in vivo while preserving the anti-tumor activity of CAR-T cells. Upon excessive activation of CAR-T cells during tumor therapy, the increased reductive environment on the T cell surface triggers the disassembly of siltuximab NGs, releasing siltuximab monomers to inhibit CRS in situ. In a CAR-T cell-mediated CRS mice model, CAR-T@NGs effectively alleviated CRS-related symptoms, such as high fever, weight loss, vascular leakage, coagulation dysfunction, and neurotoxicity. Furthermore, NGs administered in vivo did not cause organ damage and provided a safe and timely treatment for CRS.

To address the limitations of conventional nanotechnology-based drug delivery systems, this work developed enzyme and reduction dual-responsive polymeric micelles. These micelles were synthesized with copolymers composed of TPGS₃₃₅₀-PVGLIG-DOX (TPD) and FA-SS-DOX (FSD), which endow them with tumor-targeted drug delivery capabilities. TPGS₃₃₅₀ contributes to extending the circulation of micelles in body, augmenting their accumulation in tumor tissues via the enhanced permeability and retention (EPR) effect. Upon localized the tumor site, matrix metalloproteinase 2 (MMP2) cleaves the PVGLIG peptide moiety within the micelles, thereby releasing TPGS₃₃₅₀ and exposing the targeting ligand of folate. This approach enables the subsequent internalization of the micelles by tumor cells through folate receptor-mediated endocytosis. After internalization, the high intracellular concentration of glutathione (GSH) triggers the reduction of the disulfide bond within the FA-SS-DOX, leading to the release of the anticancer-drug doxorubicin (DOX), which promotes apoptosis in the tumor cells and enhances the efficacy of chemotherapy.

Phototheranostics is an emerging field in synergistic antitumor therapy in which irradiation and sensitizers are combined to produce reactive oxygen species (ROS), bio-images, and high temperatures. All of these are arrived from the energy of sensitizers, which located in excited single state (S₁). Undeniably, the decentralization of the S₁ population indirectly decreases the effect of each individual treatment. In this study, a strategy was proposed for enhancing the S₁ population, and a sensitizer with mitochondrial targeting property, 1,4-indolyl iodinated pyrrolo[3,2-b]pyrrole derivative (2I-TPIS), was assembled into adenosine triphosphate (ATP)-responsive nanoparticles (DPA-2I NPs) to achieve dual responses to irradiation and ultrasonication (US) for application to photo-sonodynamic therapy (PSDT). Compared with monotherapies, 2I-TPIS generated more ROS in PSDT, inducing mitochondrial autophagy and apoptosis, which in turn triggered immunogenic cell death (ICD). Subsequently, DPA-2I NPs were constructed and self-assembled with the chemotherapeutic agents DPA-Cd and 2I-TPIS to achieve a triple synergistic strategy involving chemotherapy (CT) and PSDT. DPA-2I NPs exhibited absolute sensitization, intra-tumoral overexpression of ATP, and disassembly. Importantly, the biosafety and potent antitumor efficiency of the DPA-2I NP-based “PSDT + CT” therapy were revealed using a 4T1 tumor model. The study results provide insights into the design of sensitizers possessing a sufficient S₁ population and a highly efficient tumor ablation capacity derived from molecular structural modulation, further enabling triple synergistic antitumor therapies, and expanding the clinical application of sensitizers.

Electrocatalytic nitrate reduction to ammonia (NO₃⁻RR) for removing nitrate from wastewater is a promising but challengeable technology that is increasingly studied. Herein, we developed an efficient CuO_x and CoCuO_x composed hybrid catalyst (CoCuO_x@CuO_x/copper foam (CF)), characteristic of distinctive shell–core nanowires grown on CF substrate with CuO_x core and CoCuO_x shell. The built-in electric field formed at the interface of the CoO/Cu₂O heterostructure promotes NO₃⁻ adsorption by modulating the charge distribution at the interface, which greatly improves the ammonia yield rate and Faradaic efficiency. At −0.2 V vs. reversible hydrogen electrode (RHE), CoCuO_x@CuO_x/CF achieves not only an excellent ammonia yield rate of up to 519.1 μg·h⁻¹·cm⁻² and Faradaic efficiency of 99.83% at 1 mM NO₃⁻ concentration, but also excellent mechanical stabilities. This study provides a novel pathway to design electrocatalyst for the removal of nitrate from dilute nitric acid solutions (≤ 2 mM).

A cutting-edge method known as photocatalytic antibacterial technology can effectively eliminate drug-resistant bacterial strains and boast a wide-ranging antimicrobial capability. In the study, a novel Ag NPs/TiO₂/PEG/PVP (ATPP) aerogel photocatalyst was synthesized by an electron beam in-situ radiation method using polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), AgNO₃, and TiO₂ as raw materials. ATPP was characterized by X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS) and solid ultraviolet diffuse reflectance spectroscopy (UV–Vis DRS). The results demonstrated that silver ions were reduced to silver nanoparticles by electron beam radiation method. At the same time, the doping of silver nanoparticles (Ag NPs) enhanced visible-light adsorption. The degradation rate of methylene blue (MB) on 5% (in mass) ATPP could reach 81% under visible light for 180 min. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used as model bacteria to explore the antimicrobial properties of ATPP by zone of the inhibition method, plate counting method and live/dead bacterial staining. Cyclic antibacterial experiments showed that the antibacterial effect of ATPP was sustainable. Meanwhile, MTT assay and Hoechst33342/PI double staining were used to prove that the composite had good biocompatibility. The aerogel photocatalytic material has the potential to decrease microbial presence in both medical and environmental settings, making it a valuable tool for such applications.

Recently, the incidence of cancer keeps increasing, seriously endangers human health, and has evolved into the main culprit of human death. Conventional chemotherapeutic drugs, such as paclitaxel and doxorubicin (DOX), have some disadvantages, including low therapeutic effect, poor water solubility, high toxic side effects, short blood circulation time in the body, and so on. To improve the anti-tumor effect of the drug in vivo and reduce its side effects on the body, researchers have designed and developed a variety of responsive nanocarriers. In this work, we synthesized D-α-tocopherol polyethylene glycol 3350 succinate (TPGS₃₃₅₀)-Gly-Pro-Leu-Gly-Val-Arg (GPLGVR)-DOX (TPD) prodrugs in response to extracellular enzymes of matrix metalloproteinase (MMP-9) in the tumor microenvironment and FA-Asp-Glu-Val-Asp (DEVD)-DOX (FPD) prodrugs responsive to intracellular enzymes of caspase-3. Then, intracellular and extracellular enzyme-responsive TPD&FPD micelles with DOX (TPD&FPD&D) were successfully prepared through dialysis method. The outer layer of TPGS₃₃₅₀ can prolong the blood circulation time of micelles in vivo, followed by accumulation of micelles at tumor tissue through enhanced permeability and retention (EPR) effect. The peptide of GPLGVR can be cleaved by MMP-9 enzymes to remove the outer layer of TPGS₃₃₅₀, exposing the targeting molecule of folate, and then the micelles are engulfed by tumor cells through folate receptor-mediated endocytosis. After entering the tumor cells, the free DOX loaded in the micelles is released, which induces tumor cell apoptosis to activate caspase-3 in the cells, cutting the peptide DEVD to accelerate the intracellular release of the DOX, which further enhances cytotoxicity to improve antitumor effect.