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.

Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerged as a promising strategy for cancer therapy. Herein, tumor microenvironment (TME) sensitive nanocarriers based on doxorubicin hydrochloride (DOX), NIR emitting carbon dots (C-dots), hollow mesoporous silica nanoparticles (HMSN) and anionic polymer citraconic anhydride-modified polylysine (PLL(cit)) are fabricated for imaging guided drug delivery. The NIR emitting C-dots were conjugated onto the surface of HMSN via disulfide bonds which can be reduced by intracellular glutathione (GSH) and result in the release of DOX into cells. And then the PLL(cit) was grafted on the surface of the nanocarriers to endow the nanocarriers with charge convertible property in mildly acidic TME (pH = 6.50) which results in prolonged blood circulation time and enhanced cellular internalization. The in vitro and in vivo experiments confirmed that the dual pH/GSH responsive features of nanocarriers can eliminate the tumor tissues effectively and elicit much slighter side effects. Moreover, since the fluorescence of C-dots can be recovered after the reduction of disulfide bonds and selectively accumulation of nanocarriers around tumor tissue, the DOX@HMSN-SS-C-dots-PLL(cit) can be served as a promising NIR fluorescence probe for targeted imaging of tumor tissue. As a kind of multifunctional nanocarrier with NIR fluorescent imaging and therapeutic functions, the theranostic nanocarriers hold great potential for tumor therapy and in vivo imaging of tumor tissue.