Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O 2 molecules to produce highly cytotoxic singlet oxygen (1 O 2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn 3 [Co(CN) 6 ] 2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O 2 generation through the reaction between endogenous H 2 O 2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.

Photodynamic therapy (PDT), a wellknown clinical modality that involves photosensitizer, molecular oxygen (O 2 ), and excitation light to generate cytotoxic reactive oxygen species such as singlet oxygen ( 1 O 2 ), has been proven to be a selective method for treating a wide spectrum of localized and superficial cancers or other diseases. [1][2][3][4][5][6][7][8][9] In addition to destroying cancer cells through direct photodamage, PDT can also induce vascular damage in the tumor, and activate the response of immune system. [10][11][12][13] Possessing spatial and temporal control over the localization of the light irradiation, the O 2 -involved PDT can remarkably improve the selectivity and reduce the side effects when compared to other conventional modalities such as chemotherapy, surgery, and radiotherapy. [14][15][16] On the other hand, tumor hypoxia compromises therapeutic effect of PDT, as O 2 is an indispensable element during the process. Uncontrollable growth of tumor cells as well as dysregulated formation of tumor blood vessels inevitably result in the cancer hypoxia. [17,18] In addition, microvascular collapse caused by PDT would further compromise the O 2 supply and aggravate the hypoxia condition, thus preventing effective PDT of cancer. Consequently, a vicious circle occurs, as PDT not only consumes localized O 2 , but also cuts off the O 2 supply. [19][20][21] To date, three main strategies have been employed to overcome the pre-existing hypoxia and improve the therapeutic effect of PDT. The most popular approach relies on the integration of PDT with other therapeutic modalities for a synergistic therapy. [17,22,23] However, such complex structures are often costly, which limit their scalable production and reproducibility. Another strategy is the utilization of intelligent nanomaterials that can act as O 2 carriers for direct transportation of mole cular oxygen to tumor sites. For example, Hu and coworkers reported photosensitizer-loaded perfluorocarbon nanodroplets as an O 2 self-enriched PDT nanoplatform. [24] The last approach is to construct smart nanoplatforms for in situ generation of O 2 within solid tumors based on the characteristics Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen ( 1 O 2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O 2 to enhancethe PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O 2 generation through the...

Nanomaterials with enzyme‐mimicking activity (nanozymes) show potential for therapeutic interventions. However, it remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, we present a new strategy based on a single‐site cascade enzymatic reaction for tumor‐specific therapy that avoids off‐target toxicity to normal tissues. A copper hexacyanoferrate (Cu‐HCF) nanozyme with active single‐site copper exhibited cascade enzymatic activity within the tumor microenvironment: Tumor‐specific glutathione oxidase activity by the Cu‐HCF single‐site nanozymes (SSNEs) led to the depletion of intracellular glutathione and the conversion of single‐site CuII species into CuI for subsequent amplified peroxidase activity through a Fenton‐type Harber–Weiss reaction. In this way, abundant highly toxic hydroxyl radicals were generated for tumor cell apoptosis. The results show that SSNEs could amplify the tumor‐killing efficacy of reactive oxygen species and suppress tumor growth in vivo.

This study was aimed at assessing the spatial and temporal distribution of surface water quality variables of the Xin’anjiang River (Huangshan). For this purpose, 960 water samples were collected monthly along the Xin’anjiang River from 2008 to 2017. Twenty-four water quality indicators, according to the environmental quality standards for surface water (GB 3838-2002), were detected to evaluate the water quality of the Xin’anjiang River over the past 10 years. Principal component analysis (PCA) was used to comprehensively evaluate the water quality across eight monitoring stations and analyze the sources of water pollution. The results showed that all samples could be analyzed by three main components, which accounted for 87.24% of the total variance. PCA technology identified important water quality parameters and revealed that nutrient pollution and organic pollution are major latent factors which influence the water quality of Xin’anjiang River. It also showed that agricultural activities, erosion, domestic, and industrial discharges are fundamental causes of water pollution in the study area. It is of great significance for water quality safety management and pollution control of the Xin’anjiang River. Meanwhile, the inverse distance weighted (IDW) method was used to interpolate the PCA comprehensive score. Based on this, the temporal and spatial structure and changing characteristics of water quality in the Xin’anjiang River were analyzed. We found that the overall water quality of Xin’anjiang River (Huangshan) was stable from 2008 to 2017, but the pollution of the Pukou sampling point was of great concern. The results of IDW helped us to identify key areas requiring control in the Xin’anjiang River, which pointed the way for further delicacy management of the river. This study proved that the combination of PCA and IDW interpolation is an effective tool for determining surface water quality. It was of great significance for the control of water pollution in Xin’anjiang River and the reduction of eutrophication pressure in Thousand Island Lake.

Dauricine, a bioactive component of Asiatic Moonseed Rhizome, has been widely used to treat a large number of inflammatory diseases in traditional Chinese medicine. In our study, we demonstrated that dauricine inhibited colon cancer cell proliferation and invasion, and induced apoptosis by suppressing nuclear factor-kappaB (NF-kappaB) activation in a dose- and time-dependent manner. Addition of dauricine inhibited the phosphorylation and degradation of IkappaBalpha, and the phosphorylation and translocation of p65. Moreover, dauricine down-regulated the expression of various NF-kappaB-regulated genes, including genes involved cell proliferation (cyclinD1, COX2, and c-Myc), anti-apoptosis (survivin, Bcl-2, XIAP, and IAP1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that dauricine significantly suppressed colonic tumor growth. Taken together, our results demonstrated that dauricine inhibited colon cancer cell proliferation, invasion, and induced cell apoptosis by suppressing NF-kappaB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of dauricine in preventing or treating colon cancer through modulation of NF-kappaB singling pathway.