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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 H 2 O 2 in acidic microenvironments to increase O 2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO 2 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 O 2 to 1 O 2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

In this work, BaYF 5 :20%Yb 3+ /2%Er 3+ / x %Bi 3+ (abbreviated as BaYF 5 :Yb,Er,Bi x , where x = 0-3.0) upconversion nanoparticles (UCNPs) with various doping concentrations of Bi 3+ were synthesized through a simple hydrothermal method. The influence of the doping amount of Bi 3+ on the microstructures and upconversion luminescence (UCL) properties of the BaYF 5 :Yb,Er,Bi x UCNPs was studied in detail. The doping concentration of Bi 3+ has little influence on the microstructures of the UCNPs but significantly impacts their UCL intensities. Under excitation of a 980 nm near-IR laser, the observed UCL intensities for the BaYF 5 :Yb,Er,Bi x UCNPs display first an increasing trend and then a decreasing trend with an increase in the ratio x , giving a maximum at x = 2.5. A possible energy-transfer process and simplified energy levels of the BaYF 5 :Yb,Er,Bi x UCNPs were proposed. The potential of the BaYF 5 :Yb,Er,Bi x UCNPs as contrast agents for computerized tomography (CT) imaging was successfully demonstrated. An obvious accumulation of BaYF 5 :Yb,Er,Bi x in tumor sites was achieved because of high passive targeting by the enhanced permeability and retention effect and relatively low uptake by a reticuloendothelial system such as liver and spleen. This work paves a new route for the design of luminescence-enhanced UNCPs as promising bioimaging agents for cancer theranostics.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO 2.9 -WSe 2 -PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H 2 O 2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.

The radioresistance of tumor cells is considered to be an Achilles' heel of cancer radiotherapy. Thus, an effective and biosafe radiosensitizer is highly desired but hitherto remains a big challenge. With the rapid progress of nanomedicine, multifunctional inorganic nanoradiosensitizers offer a new route to overcome the radioresistance and enhance the efficacy of radiotherapy. Herein, poly(vinylpyrrolidone) (PVP)-modified Bi 2 WO 6 nanoplates with good biocompatibility were synthesized through a simple hydrothermal process and applied as a radiosensitizer for the enhancement of radiotherapy for the first time. On the one hand, the high- Z elements Bi ( Z = 83) and W ( Z = 74) endow PVP-Bi 2 WO 6 with better X-ray energy deposition performance and thus enhance radiation-induced DNA damages. On the other hand, Bi 2 WO 6 semiconductors exhibit significant photocurrent and photocatalytic-like radiocatalytic activity under X-ray irradiation, giving rise to the effective separation of electron/hole (e - /h + ) pairs and subsequently promoting the generation of cytotoxic reactive oxygen species, especially hydroxyl radicals ( • OH). The γ-H2AX and clonogenic assays demonstrated that PVP-Bi 2 WO 6 could efficiently increase cellular DNA damages and colony formations under X-ray irradiation. These versatile features endowed PVP-Bi 2 WO 6 nanoplates with enhanced radiotherapy efficacy in animal models. In addition, Bi 2 WO 6 nanoplates can also serve as good X-ray computed tomography imaging contrast agents. Our findings provide an alternative nanotechnology strategy for tumor radiosensitization through simultaneous radiation energy deposition and radiocatalysis.