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The exceptional biocompatibility of Zn-based single-atom nanozymes (SAzymes) has led to extensive research in their application for disease diagnosis and treatment. However, the fully occupied 3d 10 electron configuration has seriously hampered the enzymatic-like activity of Zn-based SAzymes. Herein, a B-doped Zn-based SAzymes is fabricated by carbonizing zeolite-like Zn-based boron imidazolate framework at different temperatures (Zn-SAs@BNC x , x = 800, 900, 1000, and 1100 °C). The formed B─N bond yielded a local electric field, which changes the position of the d-band center and improved the oxidation state of Zn by facilitating the electron transfer from Zn to N to B. These changes enhanced the adsorption and activation of H 2 O 2 and O 2 by Zn-SAs@BNC 1000 , increasing the nanozymes' multi-enzyme catalytic activity. B doping led to 24.81-, 32.37-, and 13.98-fold increase in the peroxidase-, oxidase- and catalase-like, respectively, catalytic efficiency (K cat /K m ) of Zn-SAs@BNC 1000 when compared with no B doping. In addition, Zn-SAs@BNC 1000 showed excellent ability to kill tumor cells both in vitro and in vivo. This study demonstrates that the modulation of the electron configuration of Zn is an effective strategy to develop efficient anti-tumor approaches by boosting the enzymatic activity of Zn-based SAzymes., (© 2024 Wiley‐VCH GmbH.)

The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O 2 , while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808 nm laser source, the O 2 and free photosensitizer produced 1 O 2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis., (© 2024 Wiley‐VCH GmbH.)

Herein, carbon dot (CD)-supported Fe single-atom nanozymes with high content of pyrrolic N and ultrasmall size (ph-CDs-Fe SAzyme) are fabricated by a phenanthroline-mediated ligand-assisted strategy. Compared with phenanthroline-free nanozymes (CDs-Fe SAzyme), ph-CDs-Fe SAzyme exhibit higher peroxidase (POD)-like activity due to their structure similar to that of ferriporphyrin in natural POD. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analyses show that metal Fe is dispersed in ph-CDs-Fe SAzyme as single atoms. Steady-state kinetic studies show that the maximum velocity (V max ) and turnover number (k cat ) of H 2 O 2  homolytic cleavage catalyzed by ph-CDs-Fe SAzyme are 3.0 and 6.2 more than those of the reaction catalyzed by CDs-Fe SAzyme. Density functional theory (DFT) calculations show that the energy barrier of the reaction catalyzed by ph-CDs-Fe SAzyme is lower than that catalyzed by CDs-Fe SAzyme. Antitumor efficacy experiments show that ph-CDs-Fe SAzyme can efficiently inhibit the growth of tumor cells both in vitro and in vivo by synergistic chemodynamic and photothermal effects. Here a new paradigm is provided for the development of efficient antitumor therapeutic approaches based on SAzyme with POD-like activity., (© 2023 Wiley-VCH GmbH.)

Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully employed for intra-articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra-articular injection into the knee-joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee-joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell-free degradation of PNTs upon incubation with the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A gain-of-function mutant of the lymphoid phosphatase Lyp (PTPN22) has recently been implicated in type 1 diabetes and other autoimmune diseases, suggesting that small-molecule inhibitors of Lyp could be useful for the treatment of autoimmunity. Virtual ligand screening (VLS) was applied in the search for hit compounds. Two different docking algorithms, FlexX and ICM, were used to screen a library of 'drug-like' molecules against two different 3D structures, representing the catalytic site of Lyp in both the inactive 'open' and active 'closed' conformations. The top-scoring compounds of each VLS run were tested for their inhibitory activity against recombinant Lyp. Interestingly, VLS with both active and inactive conformations yielded very potent hits, with IC(50) values in the sub- and low-micromolar range. Moreover, many of these hits showed high docking scores only with one conformation. For instance, this was the case with several 2-benzamidobenzoic acid derivatives, which specifically docked into the inactive open form. Tryptophan fluorescence measurements further support a binding mode in which these compounds seem to stabilize the phosphatase in its inactive conformation.