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Radiotherapy (RT) mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death (ICD), which releases damaged-associated molecular patterns and generates "eat me" signals for the innate immune system to modulate the immunogenicity. However, tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction. Herein, Au@Bi2Te3-polyethylene glycol (PEG) was rationally constructed as theranostic nanozymes for mild photothermal therapy, tumor hypoxia modulation, and RT adjuvant cancer immunotherapy. The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species (ROS) generation, but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1 (PD-L1) to unleash immune-enhancing T cells. Moreover, Au@Bi2Te3-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy + RT to inhibit the tumor immune escape and improve antitumor immune response. Increased amounts of CD4+ and CD8+ T cells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors. Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle (NP) accumulation and oxygenation status at tumor sites. Collectively, Au@Bi2Te3-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mild-photothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties. [ABSTRACT FROM AUTHOR]

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS–NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS–NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS–NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS–NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS–NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis. [ABSTRACT FROM AUTHOR]

Ternary copper-based chalcogenide nanomaterials have become rather attractive due to the near-infrared (NIR) response in cancer theranostic fields. However, it is still challenging to further improve the theranostic efficiency of these nanomaterials. Herein, Cu-Sb-S nanoparticles (NPs) around 24 nm are synthesized facilely and functionalized with poly(vinylpyrrolidone) (PVP). Under the NIR irradiation, the resultant PVP-Cu-Sb-S NPs exhibit a relatively high photothermal conversion efficiency of 53.16% and a simultaneous reactive oxygen species (ROS) generation effect. Due to these outstanding photothermal/photodynamic effects, excellent tumor ablation results can be achieved by the combination of PVP-Cu-Sb-S NPs and 808 nm NIR laser treatments without obvious side effect. In addition, they show remarkable contrast enhancement according to in vitro and in vivo photoacoustic (PA) imaging. These PVP-Cu-Sb-S NPs could be served as a multifunctional nanotheranostic agent for PA imaging, photothermal/photodynamic cancer therapy. Statement of Significance Highly theranostic efficiency ternary copper-based chalcogenide nanomaterials has not been fully developed yet. Herein we report the PVP-Cu-Sb-S nanoparticles (NPs) with relatively high photothermal efficiency, simultaneous reactive oxygen species generation effect and photoacoustic imaging capability. The photothermal conversion efficiency of PVP-Cu-Sb-S NPs is higher than most of copper-based chalcogenide nanomaterials reported before. These findings provide a new kind of ternary copper-based chalcogenide with an enhanced theranostic effect, which could be served as a promising multifunctional nanotheranostic agent in the field of biomedical application. [ABSTRACT FROM AUTHOR]

In this study, fluorescent/magnetic dual-functional hollow nanospheres conducted by ternary CdMnS nanoparticles were synthesized via a facile Ostwald-ripening process. The as-prepared hollow nanospheres exhibited bright and tunable emission under excitation with a 365 nm UV light coupled with a strong MR signal, suggesting their promising applications in bioimaging. [ABSTRACT FROM AUTHOR]

AbstractThe aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose in high-fat diet (HFD)-fed mice. MG treatment inhibited beta-cell apoptosis in HFD-treated mice. In vitro, MG protected INS-1 cells against apoptosis and impairment of insulin secretion following High glucose/Palmitic acid (HG/PA) treatment. MG treatment enhanced autophagy flux which was blocked by HG/PA treatment. Inhibition of autophagosome formation by 3-Methyladenine or blockade of autolysosome by Chloroquine reversed the protective effects of MG on INS-1 cells. MG treatment increased AMPK phosphorylation and reduced mTOR activation in INS-1 cells. Administration of the AMPK blocker abrogated MG-induced autophagy, and similar results were observed in INS-1 cells after cotreatment with MG and mTOR activator. In conclusion, MG ameliorated pancreatic beta-cell injury induced by glucolipotoxicity through modulation of autophagy via the AMPK-mTOR pathway. [ABSTRACT FROM AUTHOR]

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS 2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vi vo without obvious side effects. We revealed that CuS-NiS 2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS 2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS 2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS 2 , which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

With a high incidence and high mortality rate, ovarian cancer presents a challenge for clinical practice. It is thus extremely urgent to investigate new diagnosis and therapy methods for the treatment of ovarian cancer. Ternary copper-based chalcogenide nanomaterials are attractive owing to their near infrared (NIR) response for cancer theranostic fields. However, improving the theranostic efficiency of these nanomaterials is challenging. Herein, CuS-MnS2 nano-flowers were easily synthesized and under NIR irradiation exhibited a relatively high photothermal conversion efficiency of 67.5% and a simultaneous reactive oxygen species (ROS) generation effect. Owing to these outstanding photothermal/photodynamic effects, excellent tumor ablation results could be achieved by the combined use of CuS-MnS2 nano-flowers and 808 nm NIR laser treatments. The main anticancer mechanism of CuS-MnS2 nano-flowers + NIR was likely necroptosis. In addition, the nano-flowers showed remarkable contrast enhancement according to magnetic resonance imaging (MRI). These CuS-MnS2 nano-flowers could thus serve as a promising multifunctional nanotheranostic agent for MRI and as a photothermal/photodynamic cancer therapy agent through necroptosis.