As prospective alternatives for natural enzymes, catalytically active nanomaterials, known as "nanozymes" have attracted considerable interest over the past decade owing to their obvious

normal cells and is more sensitive to reactive oxygen species (ROS) elevation has attracted considerable attention. [1] From this perspective, ROS-generating approaches have been widely explored as a weapon to directly or indirectly kill cancer cells; these include photodynamic therapy (PDT), [2] radiodynamic therapy (RT), [3] sonodynamic therapy (SDT), [4] and chemodynamic therapy (CDT). [5] Promoted by recent advancements in nanochemistry and nanocatalysis, a variety of nanosystems with enzyme-like activities, also called "nanozymes," have been successfully fabricated and applied in various biomedical applications. [6] Among these applications, nanozyme-initiated CDT (NCDT) is emerging as a novel cancer treatment strategy with the potential to mitigate undesired side effects. NCDT is a highly tumor-specific modality for cancer therapy triggered by peroxidase (POD)-like nanozyme-mediated chemical reactions, that is, in situ catalysis of endogenous hydrogen peroxide (H 2 O 2 ) into highly toxic hydroxyl radicals ( • OH) to induce cell apoptosis and necrosis. Although many nanomaterials, including ferromagnetic nanoparticles (γ-Fe 2 O 3 or Fe 3 O 4 ), [7] vanadium oxides, [8] copper oxide, [9] and cerium oxide (CeO 2 ), [10] have revealed POD-like activity for cancer diagnosis Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by the poor catalytic efficiency of nanozymes, insufficient endogenous hydrogen peroxide (H 2 O 2 ) content, and its off-target consumption. Herein, the authors developed a hollow mesoporous Mn/Zrco-doped CeO 2 tandem nanozyme (PHMZCO-AT) with regulated multi-enzymatic activities, that is, the enhancement of superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibition of catalase (CAT)-like activity. PHMZCO-AT as a H 2 O 2 homeostasis disruptor promotes H 2 O 2 evolution and restrains off-target elimination of H 2 O 2 to achieve intensive NCDT. PHMZCO-AT with SOD-like activity catalyzes endogenous superoxide anion (O 2 •− ) into H 2 O 2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H 2 O 2 to H 2 O. Elevated H 2 O 2 is then catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T 1 -weighted magnetic resonance imaging and X-ray computed tomography imaging are also achieved using PHMZCO-AT due to the existence of paramagnetic Mn 2+ and the high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a typical paradigm to achieve intensive NCDT efficacy by regulating multi-enzymatic activities of nanozymes to perturb the H 2 O 2 homeostasis.The ORCID identification number(s) for the author(s) of this article can be found under

Reducing the scavenging capacity of reactive oxygen species (ROS) and elevating ROS production are two primary goals of developing novel sonosensitizers for sonodynamic therapy (SDT). Hence, ultrathin 2D Bi2MoO6–poly(ethylene glycol) nanoribbons (BMO NRs) are designed as piezoelectric sonosensitizers for glutathione (GSH)‐enhanced SDT. In cancer cells, BMO NRs can consume endogenous GSH to disrupt redox homeostasis, and the GSH‐activated BMO NRs (GBMO) exhibit an oxygen‐deficient structure, which can promote the separation of electron–hole pairs, thereby enhancing the efficiency of ROS production in SDT. The ultrathin GBMO NRs are piezoelectric, in which ultrasonic waves introduce mechanical strain to the nanoribbons, resulting in piezoelectric polarization and band tilting, thus accelerating toxic ROS production. The as‐synthesized BMO NRs enable excellent computed tomography imaging of tumors and significant tumor suppression in vitro and in vivo. A piezoelectric Bi2MoO6 sonosensitizer‐mediated two‐step enhancement SDT process, which is activated by endogenous GSH and amplified by exogenous ultrasound, is proposed. This process not only provides new options for improving SDT but also broadens the application of 2D piezoelectric materials as sonosensitizers in SDT.

The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper­(II)-based tetrakis­(4-carboxy phenyl)­porphyrin (TCPP) nanoscale metal–organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224­(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T 1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224­(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.

A NO-release platform based on upconversion dendritic mesoporous silica nanocomposites was invented for combined imaging-guided synergistic chemodynamic/photodynamic/gas therapy.

The development of the advanced imaging probe holds the key to the achievement of target imaging and metastasis tracing. The bismuth based nanoprobe has been regarded as the most promising X-ray computed tomography probe due to its largest X-ray attenuation coefficient. Accordingly, the bismuth nanoparticles with controllable size distribution and light weight have been fabricated through a one pot synthesis strategy. The surface modification can be easily conducted with the polyethylene glycol to make the nanoparticles hydrosoluble and biocompatible. More importantly, the Bi nanoparticles can be excited by light to conduct excitation wavelength dependent emission in the visible (Vis) and near-infrared (NIR) region, which makes it possible to utilize it for fluorescence imaging. Under the detection of the multimode CT/fluorescence imaging, the long circulation time of the Bi nanoparticles and its specific accumulation at the liver and intestine can be visually displayed. The facile and large scale preparation method, unique luminescence property, and multimode imaging function endow the Bi nanoparticles with promising applications in clinical diagnosis.

Tailored to the peculiar tumor microenvironment, Fenton reaction-based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment. However, the efficacy of CDT is highly limited by both H 2 O 2 overproduction and the low activity of catalysts at the tumor site. Herein, a novel magnetic targeting nanoplatform (γ-Fe 2 O 3 -GOx-DMSN) has been designed by simply depositing ultrasmall γ-Fe 2 O 3 nanoparticles and natural glucose oxidase (GOx) into the large mesopores (∼13 nm) of dendritic mesoporous silica (DMSN) spheres for near-infrared (NIR) light-enhanced CDT efficacy. In this structure, GOx can effectively consume glucose in the tumor cells to induce a decrease in the pH value and generate a considerable amount of H 2 O 2 , both of which promote subsequent Fenton reaction. These ultrasmall γ-Fe 2 O 3 nanoparticles not only serve as an efficacious Fenton catalyst for degradation of the increased H 2 O 2 within the tumor to produce highly toxic hydroxyl radicals ( • OH) but also exhibit high photothermal therapy (PTT) efficiency upon irradiation with 808 nm light. Importantly, the generated hypothermia can significantly accelerate the Fenton process, thereby enabling a synergetic PTT/hypothermia-enhanced CDT effect. Our work manifests a proof of concept of H 2 O 2 -evolving and NIR-enhanced CDT, providing a new perspective for cancer therapy.

The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoO x NPs (DCDMs) with a flower-like structure fabricated by coating uniformly sized down-conversion nanoparticles (DCNPs) with dendritic mesoporous silica (DMSN) and then loading the ultrasmall oxygen-deficient molybdenum oxide nanoparticles (MoO x NPs) inside through an electrostatic interaction. Owing to the doping of Nd ions, when excited by an 808 nm laser, DCNPs emit bright NIR-II emissions (1060 and 1300 nm), which have characteristic high spatial resolution and deep tissue penetration. In terms of treatment, MoO x NPs could be specifically activated by excessive hydrogen peroxide (H2O2) in the tumor microenvironment, thus generating 1O2 via the Russell mechanism. In addition, the excessive glutathione (GSH) in the tumor cells could be depleted through the Mo-mediated redox reaction, thus effectively decreasing the antioxidant capacity of tumor cells. Importantly, the excellent photothermal properties (photothermal conversion efficiency of 51.5% under an 808 nm laser) synergistically accelerate the generation of 1O2. This cyclic redox reaction of molybdenum indeed ensured the high efficacy of tumor-specific therapy, leaving the normal tissues unharmed. MoO x NPs could also efficiently catalyze tumor endogenous H2O2 into a considerable amount of O2 in an acidic tumor microenvironment, thus relieving hypoxia in tumor tissues. Moreover, the computed tomography (CT) and T 1-weighted magnetic resonance imaging (MRI) effect from Gd3+ and Y3+ ions make DCNPs act as a hybrid imaging agent, allowing comprehensive analysis of tumor lesions. Both in vitro and in vivo experiments validate that such an “all-in-one” nanoplatform possesses desirable anticancer abilities under single laser source irradiation, benefiting from the NIR-II fluorescence/CT/MR multimodal imaging-guided photothermal/chemodynamic synergistic therapy. Overall, our strategy paves the way to explore other noninvasive cancer phototheranostics.