Metal-rich cascade nanosystem for dual-pathway ferroptosis resistance regulation and photothermal effect for efficient tumor combination therapy.

Despite the therapeutic response of ferroptosis in various tumors, ferroptosis resistance has been found in numerous studies, significantly hindering the progress of ferroptosis anti-tumor therapy. Herein, we propose a metal-rich cascade nanosystem (Simvastatin-HMPB-Mn@GOx) combined with the dual-pathway regulation of ferroptosis resistance and photothermal therapy for efficient tumor combination therapy. The manganese-bonded hollow mesoporous Prussian blue (HMPB-Mn) serves as the photothermal agent and metal donor, and dissociates multivalent metal ions Mn2+, Fe3+ and Fe2+ to consume glutathione and amplify the Fenton reaction. Glucose oxidase (GOx) absorbed serves as the converter to provide hydrogen peroxide (H2O2) for the cascade Fenton reaction, causing a high burst of hydroxyl radicals (˙OH) and lipid peroxidation. Simvastatin innovatively acts as a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) inhibitor to decrease the expression of coenzyme Q10 (CoQ10) and glutathione peroxidase 4 (GPX4), eventually defeating ferroptosis resistance. The nanosystem acted in both classical and non-classical ferroptosis pathways and showed significant ferroptosis- and hyperthermia-induced anti-tumor efficacy both in vitro and in vivo. Thus, this study offers a promising way for ferroptosis and phototherapy to achieve complete tumor regression.

Gelatin/calcium chloride electrospun nanofibers for rapid hemostasis.

Blood coagulation is the body's main defense to bleeding caused by trauma and is divided into endogenous and exogenous pathways. Calcium ions play a very important role in the process of blood coagulation, as the ions activate the many enzymes that are required for coagulation. In this paper, gelatin hemostatic membranes containing calcium ions were prepared by electrospinning. The fibers were characterized with scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The biocompatibility and coagulation processes using the calcium ion-containing gelatin fibrous membranes were evaluated in vitro with dynamic whole-blood coagulation tests, hemolysis tests, coagulation time tests, and platelet adhesion tests. It was demonstrated that the calcium ion-containing gelatin membranes had lower hemolysis rates and shorter clotting times than commercially available hemostatic sponges and hemostatic gauzes. In vivo hemostasis experiments were also conducted on the tail vein and liver of mice. Animal experiments demonstrated that the incorporation of calcium ions into the electrospun gelatin membranes promoted platelet aggregation, ensured adhesion of the electrospun membrane to the wound and reduced the bleeding volume and hemostasis time. The composite calcium ion-gelatin electrospun membranes exhibited good in vivo and in vitro hemostatic abilities and accelerated blood clotting by stimulating the coagulation pathway to promote platelet aggregation at the wounds and the formation of mature blood clots for a new approach for acute trauma treatment.