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

Therapeutic nanosystems which can be triggered by the distinctive tumor microenvironment possess great selectivity and safety to treat cancers via in situ transformation of nontoxic prodrugs into toxic therapeutic agents. Here, we constructed intelligent, magnetic targeting, and tumor microenvironment-responsive nanocatalysts that can acquire oxidation therapy of cancer via specific reaction at tumor site. The magnetic nanoparticle core of iron carbide-glucose oxidase (Fe 5 C 2 -GOD) achieved by physical absorption has a high enzyme payload, and the manganese dioxide (MnO 2 ) nanoshell as an intelligent "gatekeeper" shields GOD from premature leaking until reaching tumor tissue. Fe 5 C 2 -GOD@MnO 2 nanocatalysts maintained inactive in normal cells upon systemic administration. On the contrary, after endocytosis by tumor cells, tumor acidic microenvironment induced decomposition of MnO 2 nanoshell into Mn 2+ and O 2 , meanwhile releasing GOD. Mn 2+ could serve as a magnetic resonance imaging (MRI) contrast agent for real-time monitoring treatment process. Then the generated O 2 and released GOD in nanocatalysts could effectively exhaust glucose in tumor cells, simultaneously generating plenty of H 2 O 2 which may accelerate the subsequent Fenton reaction catalyzed by the Fe 5 C 2 magnetic core in mildly acidic tumor microenvironments. Finally, we demonstrated the tumor site-specific production of highly toxic hydroxyl radicals for enhanced anticancer therapeutic efficacy while minimizing systemic toxicity in mice.

Rare-earth-based upconversion nanotechnology has recently shown great promise for photodynamic therapy (PDT). However, the NIR-induced PDT is greatly restricted by overheating issues on normal bodies and low yields of reactive oxygen species (ROS, O). Here, IR-808-sensitized upconversion nanoparticles (NaGdF:Yb,Er@NaGdF:Nd,Yb) were combined with mesoporous silica, which has Ce6 (red-light-excited photosensitizer) and MC540 (green-light-excited photosensitizer) loaded inside through covalent bond and electrostatic interaction, respectively. When irradiated by tissue-penetrable 808 nm light, the IR-808 greatly absorb 808 nm photons and then emit a broadband peak which overlaps perfectly with the absorption of Nd and Yb. Thereafter, the Nd/Yb incorporated shell synergistically captures the emitted NIR photons to illuminate NaGdF:Yb,Er zone and then radiate ultrabright green and red emissions. The visible emissions simultaneously activate the dual-photosensitizer to produce a large amount of ROS and, importantly, low heating effects. The in vitro and in vivo experiments indicate that the dual-photosensitizer nanostructure has trimodal (UCL/CT/MRI) imaging functions and high anticancer effectiveness, suggesting its potential clinical application as an imaging-guided PDT technique.

Photodynamic therapy (PDT), as a minimally invasive and high‐efficiency anticancer approach, has received extensive research attention recently. Despite plenty of effort devoted to exploring various types of photodynamic agents with strong near‐infrared (NIR) absorbance for PDT and many encouraging progresses achieved in the area, effective and safe photodynamic photosensitizers with good biodegradability and biocompatibility are still highly expected. In this work, a novel nanocomposite has been developed by assembly of iron oxide (Fe3O4) nanoparticles (NPs) and Au nanoparticles on black phosphorus sheets (BPs@Au@Fe3O4), which shows a broad light absorption band and a photodegradable character. In vitro and in vivo assay indicates that BPs@Au@Fe3O4 nanoparticles are highly biocompatible and exhibit excellent tumor inhibition efficacy owing to a synergistic photothermal and photodynamic therapy mediated by a low‐power NIR laser. Importantly, BPs@Au@Fe3O4 can anticipatorily suppress tumor growth by visualized synergistic therapy with the help of magnetic resonance imaging (MRI). This work presents the first combination application of the photodynamic and photothermal effect deriving from black phosphorus nanosheets and plasmonic photothermal effect from Au nanoparticles together with MRI from Fe3O4 NPs, which may open the new utilization of black phosphorus nanosheets in biomedicine, optoelectronic devices, and photocatalysis.

The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO 2 ) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME-enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO 2 ) with covalently loaded chlorin e6 are obtained as near-infrared light mediated PDT agents, and then a mMnO 2 shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO 2 degrades rapidly within the TME, releasing Mn 2+ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a selfenhanced imaging. Significantly, the degradation of mMnO 2 shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H 2 O 2 and reduction of glutathione, thus achieving a highly potent chemo-photodynamic therapy.