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Abstract Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer‐associated fibroblasts (CAFs) show multiple tumor‐promoting effects and can induce tumor immune evasion and drug‐resistance. Regulating CAFs can be a potential strategy to augment systemic anti‐tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs’ tumor‐promoting and immune‐suppressive phenotypes. Accordingly, a controllable and TME‐responsive hydrogen therapy based on a CaCO3 nanoparticles‐coated magnesium system (Mg‐CaCO3) is developed. The hydrogen therapy by Mg‐CaCO3 can not only directly kill tumor cells, but also inhibit pro‐tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg‐CaCO3 can significantly suppress tumor growth, turn the “cold” primary tumor into “hot”, and stimulate systematic anti‐tumor immunity, which is confirmed by the bilateral tumor transplantation models of “cold tumor” (4T1 cells) and “hot tumor” (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti‐tumor immune stimulating strategy by remodeling tumor stromal microenvironment.

With the clinical prevalence of drug-resistant pathogenic bacteria, developing non-antibiotic strategies to treat multi-drug-resistant bacterial infections is urgent yet challenging. Ferroptosis is a non-apoptotic form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis-like for anti-infection therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, CuFeS2 nanozyme is revealed as a ferroptosis-like initiator to eradicate bacterial infections for effective anti-infection therapy. Upon activating by visible light irradiation or hydrogen peroxide, the as-prepared CuFeS2 nanozyme can significantly expedite reactive oxygen species generation, deplete intracellular glutathione, and interfere with respiratory metabolisms, resulting in lipid peroxidation-driven ferroptotic damage. Additionally, the CuFeS2 displays good photothermal conversion capacity under near-infrared light irradiation, further augmenting the antibacterial efficiency. Accordingly, the CuFeS2 nanozyme shows potent antibacterial activity against Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro. Moreover, it shows excellent biocompatibility and robust anti-infection effects in MRSA-infected wounds in vivo. This ferroptosis-like antibacterial strategy may open up new insights into the treatment of drug-resistant pathogen infection.

Abstract Intervertebral disc degeneration (IVDD)‐induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism is partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it is shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress‐induced ferroptosis in nucleus pulposus (NP) cells in vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe2+ to mitigate iron overload, and regulate the expression of iron storage proteins such as ferritin heavy chain (FHC), ferritin, and transferrin receptor (TFR). More importantly, PDA NPs co‐localize with glutathione peroxidase 4 (GPX4) around the mitochondria and suppress ubiquitin‐mediated degradation, which in turn exerts a protective function via the transformation and clearance of phospholipid hydroperoxides. PDA NPs further down‐regulate malondialdehyde (MDA) and lipid peroxide (LPO) production; thus, antagonizing ferroptosis in NP cells. Moreover, PDA NPs effectively rescue puncture‐induced degeneration in vivo by targeting ferroptosis and inhibiting GPX4 ubiquitination, resulting in the upregulation of antioxidant pathways. The findings offer a new tool to explore the underlying mechanisms and a novel treatment strategy for IVDD‐induced LBP.

Abstract Background The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property. Results Herein, biocompatible Cu3SnS4 nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4 NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4 NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4 NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4 NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection. Conclusions The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4 NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment. Graphical Abstract

Abstract Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system‐related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination‐proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS‐induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation‐protective discography contrast agent.

Excessive free radicals are noxious for living organisms and lead to cell death. Destruction of malignant cells by reactive free radicals has been widely used in cancer treatment. A key consideration is how to allow targeted free radical attack on cancer cells and avoid unwanted side-effects. Herein, we develop an efficient intracellular free radical generation strategy against cancer cells by delivering active ingredients into cancer cells, where free radicals are selectively generated by a lysosomal bioactivation process. Artesunate (ART), which is non-toxic to normal cells, was chosen as the free radical source and transported into cells with a hollow mesoporous silica-based delivery system (ART@HMS). To selectively activate the ART@HMS inside cancer cells, a high-bioactive Fe/O cluster-mesoporous silica nanosystem (Fe/O-MSN) was elaborately prepared. Under the bioactivation of the lysosome, the low-dose ART@HMS together with biocompatible Fe/O-MSN induced significant intracellular generation of toxic free radicals and efficient death of cancer cells. This selective intracellular free radical generation strategy is encouraging for its development into an effective low-cost cancer therapy. [ABSTRACT FROM AUTHOR]

Free radicals are toxic entities known to cause cellular damage and to mediate cell death. We herein develop a controlled free radical generation strategy for cancer therapy via pH-responsive release of benzoyl peroxide (BPO) in tumor cells and producing free radicals to mediate cell death. BPO as the free radical resource was encapsulated into a chitosan (Cs)-coated mesoporous silica nanocomposite (BPO(aHMSNs-Cs). The mesoporous silica carrier improved the BPO solubility by preventing its crystallization and promoted its stability by inclusion. Chitosan imparted the nanocomposite pH-responsive BPO release capacity with enhanced BPO release in simulated acidic tumor media (pH 6.5) and minor release in simulated normal tissue media (pH 7.4). The enhanced free radical generation in tumor media further led to significantly higher cytotoxicity in the tumor at acidic pH 6.5 than at physiological pH 7.4. The free radical-mediated cytotoxicity of BPO@HMSNs-Cs was verified by the observation of free radical-induced green fluorescence in cells. This pH-responsive free radical generation nanocomposite may provide new opportunities for controlled drug delivery and cancer therapy. [ABSTRACT FROM AUTHOR]