Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper−amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H 2 O 2 -reinforced chemodynamic therapy for drugresistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu 2+ to Cu + . Subsequently, the generated Cu + would react with local H 2 O 2 to generate toxic hydroxyl radicals (•OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H 2 O 2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.
Numerous studies have determined that physical cues, especially the nanotopography of materials, play key roles in directing stem cell differentiation. However, most research on nanoarrays for stem cell fate regulation is based on nonbiodegradable materials, such as silicon wafers, TiO, and poly(methyl methacrylate), which are rarely used as tissue engineering biomaterials. In this study, we prepared biodegradable polylactic acid (PLA) nanopillar arrays with different diameters but the same center-to-center distance using a series of anodic aluminum oxide nanowell arrays as templates. Human adipose-derived stem cells (hADSCs) were selected to investigate the effect of the diameter of PLA nanopillar arrays on stem cell differentiation. By culturing hADSCs without the assistance of any growth factors or osteogenic-induced media, the differentiation tendencies of hADSCs on the nanopillar arrays were assessed at the gene and protein levels. The assessment results suggested that the osteogenic differentiation of hADSCs can be driven by nanopillar arrays, especially by nanopillar arrays with a diameter of 200 nm. Moreover, an in vivo animal model of the samples demonstrated that PLA film with the 200 nm pillar array exhibits an improved ectopic osteogenic ability compared with the planar PLA film after 4 weeks of ectopic implantation. This study has provided a new variable to investigate in the interaction between stem cells and nanoarray structures, which will guide the bone regeneration clinical research field. This work paves the way for the utility of degradable biopolymer nanoarrays with specific geometrical and mechanical signals in biomedical applications, such as patches and strips for spine fusion, bone crack repair, and restoration of tooth enamel.
Transition-metal nitrides have attracted a great deal of interest as electrocatalysts for water splitting due to their super metallic performance, high efficiency, and good stability. Herein, we report a novel design of hierarchical electrocatalyst based on NiFeN, where the presence of carbon fiber cloth as a scaffold can effectively alleviate the aggregation of NiFeN nanostructure and form three-dimensional conducting networks to enlarge the surface area and simultaneously enhance the charge transfer. The composition and morphological variations of NiFe precursors during annealing in different atmospheres were investigated. Such NiFeN/CC hierarchical electrocatalyst shows much improved electrochemical properties for water splitting in terms of overpotentials (105 and 190 mV at 10 mA/cm for hydrogen evolution reaction and oxygen evolution reaction, respectively) and stability.
Proinflammatory (M1) macrophages play a vital role in antitumor immunity, and regulation of proinflammatory macrophage polarization is critical for immunotherapy. The polarization of macrophages can be regulated by biological or chemical stimulation, but investigations of the regulatory effect of physical stimulation are limited. Herein, regulating macrophage polarization with localized electrical signals derived from a piezoelectric -phase poly(vinylidene fluoride) ( -PVDF) film in a wireless mode is proposed. Charges released on the surface of the -PVDF film driven by ultrasonic irradiation can significantly enhance the M1 polarization of macrophages. Mechanistic investigation confirms that electrical potentials rather than reactive oxygen species and mechanical forces enable Ca 2+ influx through voltage-gated channels and establishment of the Ca 2+ -CAMK2A-NF-B axis to promote the proinflammatory macrophage response during ultrasound treatment. Piezoelectric material-mediated electrical signal-activated proinflammatory macrophages significantly inhibit tumor cell proliferation. A method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy is provided here.
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