Co-presenting non-antibiotic drugs and pyrimidinethiol on gold nanoparticles (NPs) can generate broad-spectrum antibacterial and bactericidal activities against superbugs. Dimethylbiguanide (metformin), an anti-hyperglycemic drug, shows the best enhanced activity via increasing the ability to compromise bacterial cell walls. Synergistic effects are also reflected in the eradicating biofilm cells. Our findings suggest a large chemical space to develop new antibacterial materials to treat superbugs.

Aims: Activation of intrarenal renin-angiotensin system (RAS) has a detrimental effect on the progression of chronic kidney diseases (CKDs), although the regulation of intrarenal RAS remains unclear. The aim of the present study was to evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal RAS activation. Results: AOPPs upregulated the expression of almost all components of RAS and increased activity of angiotensin-converting enzyme in cultured proximal tubular epithelial cells. The triggering effect of AOPPalbumin was 100-times stronger than that of unmodified albumin. The effect of AOPP-albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling involving activation of protein kinase Ca, NADPH oxidase, and nuclear factor-jB/activation protein-1. Chronic AOPP-albumin loading in unilateral nephrectomy rats resulted in deposition of AOPPs in renal tubular cells accompanied with local RAS activation and functional perturbations such as increase in urinary albumin excretion. Accumulation of AOPPs was also detected in human renal tubular cells and correlated with expression of angiotensin II in renal biopsies from 19 patients with IgA nephropathy. Innovation and Conclusion: This study demonstrated for the first time that AOPPs modified albumin functions as a strong trigger of intrarenal RAS via a CD36-mediated, redox-dependent pathway. Given the fact that accumulation of AOPPs is prevalent in diabetes and CKD, targeting AOPPs could be a strategy for the therapeutic intervention of CKD. Antioxid. Redox Signal. 18,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]

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The profiling of oxidase-catalyzed biomarkers is an essential procedure for the diagnosis and precise treatment of metabolic diseases. Inspired by the metabolism of H O in peroxisomes, a novel chemiluminescent silica nanodevice (CSN) was designed for the sensitive and selective sensing of intracellular oxidase-catalyzed biomarkers. Oxidases catalyzed the oxidation of biomarkers followed by the production of H O , and then the generated H O was employed to trigger chemiluminescence of the CSN. Utilizing this nanodevice, we not only accurately quantified intracellular glucose but also developed its further application for facile insulin sensitizer screening. Furthermore, sensitive and multiparametric analysis of oxidase-catalyzed biomarkers like lactic acid, uric acid, and ethanol was demonstrated. Thus, this peroxisome-inspired CSN holds great promise for the general diagnosis of metabolic diseases and in drug discovery.

Breast cancer is the leading cancer type diagnosed in the female population, and cancer metastasis is the main reason for cancer-caused mortality. A novel nanoplatform is herein presented integrating polydopamine-functionalized nanosized reduced graphene oxide (NRGO), gold nanostars (GNS), and doxorubicin (DOX) (denoted as NRGO-GNS@DOX) for combinational treatment of metastatic breast cancer. Upon localized near infrared (NIR) laser irradiation, the NRGO-GNS@DOX nanocomposites induce significant cytotoxicity in 4T1 breast cancer cells due to a cumulative therapy effect of NRGO-GNS-elicited hyperthermia and DOX-induced cytotoxicity. Antitumor studies in orthotopic 4T1 breast tumor-bearing nude mice demonstrate that NRGO-GNS@DOX in combination with NIR laser irradiation inhibit the tumor growth and suppress the lung metastasis. Contribution of DOX-caused apoptosis of the cancer cells and hyperthermia-induced deconstruction of the tumor-associated blood vessels may account for the superior antitumor performance of the NRGO-GNS@DOX nanocomposites. These results imply a good potential of NRGO-GNS@DOX for combined photothermal and chemotherapy of the metastatic cancer.