Wenyan Yin

Photodynamic therapy (PDT) has emerged as an advanced therapeutic modality owing to its inherent merits of minimal invasiveness and precise spatiotemporal

Nanozymes suffer from insufficient catalytic activity and sluggish electron transfer, while hypoxic tumor microenvironment (TME)-induced radioresistance and limited reactive oxygen species accumulation hinder radiotherapy efficacy. Existing nanozyme radiosensitizers often require high-dose radiotherapy or combined drugs to achieve only a modest efficacy. Herein, we report a Pt-anchored MoO_x (MPP) nanozyme synthesized via a surface defect-ligand reduction strategy with Pt nanoclusters loading up to 34.39 ± 0.92 wt %. It features a gradient electron-transfer interface constructed by strong Pt–O–Mo interactions, which enables atomic-level integration of Pt⁰/Pt²⁺ nanoclusters with MoO_x and the simultaneous introduction of oxygen vacancies and an interfacial electron pool. Density functional theory calculations confirm the interface upshifts MoO_x’s d-band center, accelerates Mo → Pt electron transfer, and reduces the H₂O₂ dissociation barrier to 0.18 eV. Consequently, MPP achieves a catalase-like specific activity of 3884.53 U mg^–1 (2-fold natural catalase, 7528-fold MnO₂) and a turnover number (TON) of 25.7021 s^–1. Additionally, MPP exhibits a quantitative factor for electron transfer efficiency of 1.75, exceeding reported nanozymes. In the acidic TME, MPP orchestrates a catalase/superoxide dismutase/oxidase cascade to relieve hypoxia and generate ^•O₂^–/¹O₂. Synergized with Pt’s high-Z effect, MPP amplifies the efficacy of 6 Gy with low-dose radiotherapy, achieving 75.24% tumor inhibition rate without inducing systemic toxicity. This gradient electron-transfer interface strategy provides a promising paradigm for high-efficacy, low-toxicity tumor-specific therapy.

Addressing the stability-activity imbalance of natural enzyme-nanozyme self-cascade catalysis for tumor-specific therapy while inhibiting tumor metastasis via multiple killing mechanisms remains a challenge. Herein, we constructed a tumor microenvironment (TME)-responsive mannose-modified MoS₂-tannic acid (TA)-Fe-glucose oxidase (GOx) nanoreactor (MTFGM) via a spatial confinement strategy relying on metal-polyphenol coordination and electrostatic interactions for addressing this issue. GOx was confined on MoS₂ via hydrogen bonds and π-π stacking. TA's polyphenol network and mannose's shielding effect enhanced GOx stability by preventing off-target catalysis, while TA-Fe on MoS₂ boosted peroxidase (POD)-like catalytic activity by facilitating Fe³⁺/Fe²⁺ electron transfer for cocatalysis. In the TME, GOx depleted glucose to self-supply H₂O₂ and gluconic acid, which activated the POD-like activity of MTFGM to decompose H₂O₂ into toxic hydroxyl radicals (^•OH) with a maximum reaction rate 4-fold higher and turnover number 170-fold higher than pristine MoS₂. Simultaneously, MoS₂-TA-Fe's glutathione peroxidase-like activity plus H₂S_n production continuously consumed glutathione (GSH) to break tumor antioxidant defense. This cascade synergistically induced four tumor-killing mechanisms: GOx-mediated metabolic starvation, ^•OH-triggered apoptosis, GSH depletion-driven ferroptosis, and cystine accumulation/H₂S_n-induced disulfidptosis collectively disrupt tumor redox homeostasis and inhibit metastasis. Our work clarifies the structure-activity relationship of confinement-based cascade nanoreactors and provides a TME-responsive multiple cell death paradigm for tumor-specific therapy.

Correction for ‘WS₂ nanosheet as a new photosensitizer carrier for combined photodynamic and photothermal therapy of cancer cells’ by Yuan Yong et al., Nanoscale, 2014, 6, 10394–10403, https://doi.org/10.1039/C4NR02453B.

Boosting catalytic activity of single‐atom nanozymes (SAzymes) to substitute natural metalloenzymes remains challenging due to the lack of enzyme‐like secondary building blocks and proper 3D conformation. Herein, a natural amino acid L‐cysteine (L‐Cys)‐triggered auto‐assembly process engineers the spatial positioning of 3D‐biomimetic S‐Cu‐S single‐atom catalytic sites and adjacent L‐Cys on sheet‐like MoS ₂ nanozyme, achieving activated MoCC SAzymes. MoCC achieves a maximum Cu single‐atom loading of 10.11% by suppressing aggregation through L‐Cys coordination. Particularly, MoCC can properly bind and react with the H ₂ O ₂ substrate, mimicking 3D catalytic pockets of natural enzymes. The maximum reaction velocity (4.56×10 ⁻⁷ M s ⁻¹ ), affinity (Michaelis constant, 0.65 mM), and specific activity (SA) (355.59 U mg ⁻¹ ) catalyzed by peroxidase (POD)‐mimicking MoCC are 16.3‐, 17.9‐, and 1.2‐fold higher than natural horseradish peroxidase (HRP). Density functional theory computations reveal that the S‐Cu‐S single‐atom catalytic sites stabilized by L‐Cys bonding function as a reversible electron flow workstation, triggering storage and transfer with MoS ₂ , facilitating swift electron exchange with H ₂ O ₂ , reducing energy barrier for hydroxyl radicals generation. The optimized 3D S‐Cu‐S single‐atom featuring L‐Cys building of MoCC exhibits cascaded catalase‐like activity and sono‐piezocatalysis effect, non‐invasively amplifying the generation of oxygen and singlet oxygen. Consequently, multiple free radicals can selectively eliminate dental bacteria and biofilms.

Electrochemical nitrogen reduction reaction (ENRR) provides a sustainable route for the NH₃ synthesis. However, designing catalysts that facilitate efficient electron/proton transfer and the hydrogenation of multiple intermediates remains a challenge. In this study, inspired by the natural nitrogenase proteins, a biomimetic Fe-Mo diatomic catalyst (FeMo-CDW(CT-3h)) was designed for efficient ENRR. The microenvironment of Fe-Mo diatomic sites was precisely tuned using the O-induced atomic confinement effect, where O atoms modulate the activity of the sites. FeMo-CDW(CT-3h) with four O atoms achieves a record-breaking NH₃ yield at universal pH as well as high stability (250 h and 10 cycles) due to its optimal electron transfer efficiency. In particular, the NH₃ yield of 336.03 μg h^-1 cm^-2 in 0.1 M HCl was over three times higher than the previously reported maximum. Theoretical calculations reveal that the hybridization of Fe-Mo d orbitals with N₂* antibonding orbitals enhances electron transfer, extends and weakens the N≡N bond, and accelerates proton transfer and hydrogenation, thereby increasing NH* antibonding orbitals enhances electron transfer, extends and weakens the N≡N bond, and accelerates proton transfer and hydrogenation, thereby increasing NH₃ generation.

With the rapid development of nanotechnology and nanomedicine, there are great interests in employing nanomaterials to improve the efficiency of disease diagnosis and treatment. The clinical translation of hafnium oxide (HfO₂), commercially namedas NBTXR3, as a new kind of nanoradiosensitizer for radiotherapy (RT) of cancers has aroused extensive interest in researches on Hf‐based nanomaterials for biomedical application. In the past 20 years, Hf‐based nanomaterials have emerged as potential and important nanomedicine for computed tomography (CT)‐involved bioimaging and RT‐associated cancer treatment due to their excellent electronic structures and intrinsic physiochemical properties. In this review, a bibliometric analysis method is employed to summarize the progress on the synthesis technology of various Hf‐based nanomaterials, including HfO₂, HfO₂‐based compounds, and Hf‐organic ligand coordination hybrids, such as metal‐organic frameworks or nanoscaled coordination polymers. Moreover, current states in the application of Hf‐based CT‐involved contrasts for tissue imaging or cancer diagnosis are reviewed in detail. Importantly, the recent advances in Hf‐based nanomaterials‐mediated radiosensitization and synergistic RT with other current mainstream treatments are also generalized. Finally, current challenges and future perspectives of Hf‐based nanomaterials with a view to maximize their great potential in the research of translational medicine are also discussed.

Machine learning motivated Cu@MoS ₂ catalysts design for enhanced peroxidase-like activity.

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoO_x-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoO_x nanoparticles to catalyze the decomposition of H₂O₂ in acidic microenvironments to increase O₂ production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO₂ nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoO_x disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O₂ to ¹O₂ for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.