Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO₂ nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se^2-, to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO₂ nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO₂ nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO₂ nanocomposite. The morphology of porous Se@SiO₂ nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO₂ nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO₂ nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO₂ nanocomposite. Results: In vitro, intervention with porous Se@SiO₂ nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H₂O₂-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO₂ nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO₂ nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO₂ nanocomposite may provide clinic benefit for bone tissue engineering.

We herein explored a smart Fe-HPPy@Au/DOX theranostic agent for CT diagnosis and PTT/chemotherapy/CDT synergistic treatment of cancer. When the Fe-HPPy@Au/DOX theranostic agent entered the tumor, the tumor environment accelerated the trapped Fe ions release to catalyze the production of ˙OH for CDT. NIR irradiation drove the PTT, and at the same time improved the CDT by increasing the production of ˙OH and triggered DOX release for chemotherapy. In addition, the Au nanoparticles on the surface of Fe-HPPy@Au nanocomposites could be used as a CT imaging agent and catalyzer to produce H₂O₂ for enhanced CDT.

Chemodynamic therapy (CDT) is an emerging approach to treat cancer based on the tumor microenvironment (TME), but its limited content of endogenous hydrogen peroxide (H₂O₂) weakens the anticancer effects. Herein, a multifunctional biomimetic nanozyme (Se@SiO₂–Mn@Au/DOX, named as SSMA/DOX) is fabricated, which undergoes TME responsive self-cascade catalysis to facilitate MRI guided enhanced chemo/chemodynamic therapy. The SSMA/DOX nanocomposites (NCs) responsively degrade in acidic conditions of tumor to release Se, DOX, Au and Mn²⁺. Mn²⁺ not only enables MRI to guided therapy, but also catalyzes the endogenous H₂O₂ into hydroxyl radical (˙OH) for CDT. In addition, the Au NPs continuously catalyze glucose to generate H₂O₂, enhancing CDT by supplementing a sufficiently reactive material and cutting off the energy supply of the tumor by consuming glucose. Simultaneously, Se enhances the chemotherapy of doxorubicin hydrochloride (DOX) and CDT by upregulating ROS in the tumor cells, achieving remarkable inhibition effect towards tumor. Moreover, SSMA/DOX NCs have good biocompatibility and degradability, which avoid long-term toxicity and side effects. Overall, the degradable SSMA/DOX NCs provide an innovative strategy for tumor microenvironment responsive self-cascade catalysis to enhance tumor therapy.

Background: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous Se@SiO₂ nanoparticles (NPs) with antioxidant properties. Methods: The protective effect of Se@SiO₂ NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of Se@SiO₂ NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model. Results: This study demonstrated that Se@SiO₂ NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of Se@SiO₂ was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our Se@SiO₂ NPs in various metabolic disorders and inflammatory diseases. Conclusion: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders.