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.

In this work, a simple method is demonstrated for the synthesis of multifunctional core–shell nanoparticles NaYF4:Yb,Er@NaYF4:Yb@NaNdF4:Yb@NaYF4:Yb@PAA (labeled as Er@Y@Nd@Y@PAA or UCNP@PAA), which contain a highly effective 808‐nm‐to‐visible UCNP core and a thin shell of poly(acrylic acid) (PAA) to achieve upconversion bioimaging and pH‐sensitive anticancer chemotherapy simultaneously. The core–shell Nd3+‐sensitized UCNPs are optimized by varying the shell number, core size, and host lattices. The final optimized Er@Y@Nd@Y nanoparticle composition shows a significantly improved upconversion luminescence intensity, that is, 12.8 times higher than Er@Y@Nd nanoparticles. After coating the nanocomposites with a thin layer of PAA, the resulting UCNP@PAA nanocomposite perform well as a pH‐responsive nanocarrier and show clear advantages over UCNP@mSiO2, which are evidenced by in vitro/in vivo experiments. Histological analysis also reveals that no pathological changes or inflammatory responses occur in the heart, lungs, kidneys, liver, and spleen. In summary, this study presents a major step forward towards a new therapeutic and diagnostic treatment of tumors by using 808‐nm excited UCNPs to replace the traditional 980‐nm excitation.

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Reactive oxygen species (ROS)-based therapeutic modalities including chemodynamic therapy (CDT) and photodynamic therapy (PDT) hold great promise for conquering malignant tumors. However, these two methods tend to be restricted by the overexpressed glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Here, we develop biodegradable copper/manganese silicate nanosphere (CMSN)-coated lanthanide-doped nanoparticles (LDNPs) for trimodal imaging-guided CDT/PDT synergistic therapy. The tridoped Yb3+/Er3+/Tm3+ in the ultrasmall core and the optimal Yb3+/Ce3+ doping in the shell enable the ultrabright dual-mode upconversion (UC) and downconversion (DC) emissions of LDNPs under near-infrared (NIR) laser excitation. The luminescence in the second near-infrared (NIR-II, 1000–1700 nm) window offers deep-tissue penetration, high spatial resolution, and reduced autofluorescence when used for optical imaging. Significantly, the CMSNs are capable of relieving the hypoxic TME through decomposing H2O2 to produce O2, which can react with the sample to generate 1O2 upon excitation of UC photons (PDT). The GSH-triggered degradation of CMSNs results in the release of Fenton-like Mn2+ and Cu+ ions for •OH generation (CDT); simultaneously, the released Mn2+ ions couple with NIR-II luminescence imaging, computed tomography (CT) imaging, and magnetic resonance (MR) imaging of LDNPs, performing a TME-amplified trimodal effect. In such a nanomedicine, the TME modulation, bimetallic silicate photosensitizer, Fenton-like nanocatalyst, and NIR-II/MR/CT contrast agent were achieved “one for all”, thereby realizing highly efficient tumor theranostics.

Periodate (PI, IO 4 − ) can be activated by hydroxylamine (HA), resulting in the rapid removal of organic pollutants within seconds. While the previous studies on PI-based advanced oxidation processes (AOPs) have proposed iodate radical ( • IO 3 ) as the major reactive species, no evidence of • IO 3 production was found in the present PI/HA system. Reactive oxygen species (ROS) including • OH, HO 2• , and 1 O 2 are proposed to be the main oxidants of the PI/HA system, which is supported by various tests employing the scavengers, chemical probes, and spin-trapping electron paramagnetic resonance (EPR) technique. To minimize the risk of toxic iodinated byproduct formation caused by reactive iodine species such as HOI and I 2 , the molar ratio of HA/PI was optimized at 0.6 to achieve the stoichiometric conversion of IO 4 − to iodate (IO 3 − ), a preferred nontoxic sink of iodine species. The PI/HA system also efficiently inactivated both Gram-positive and -negative bacteria with producing 1 O 2 as the dominant disinfectant. The mechanism of ROS production was also investigated and is discussed in detail. This work offers a simple and highly efficient option for PI activation and ROS production which might find useful applications where urgent and rapid removal of toxic pollutants is needed.

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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