Extracorporeal Hemoperfusion Therapy for Sepsis: Multi-Lamellar Microspheres towards Cascade Endotoxin Removal and Broad-Spectrum Radical Eliminating

Sepsis is a life-threatening condition originated from the accumulation of endotoxin in blood in response to infection (e.g., bacterial infection, COVID-19), and then aggravating by the systemic inflammatory responses, microcirculation disorders and oxidative stress, ultimately resulting in the dysfunction of multiple organs. Herein, advanced multi-lamellar microspheres (CPG-Ln-MSs) with cascade endotoxin adsorption and oxidative stress relief functions are constructed as an alternative adsorbent for hemoperfusion therapy towards sepsis. The CPG-Ln-MSs achieve effective endotoxin absorption (nearly 455.3 EU/g) and show excellent broad-spectrum radical scavenging activity for treating oxidative stress triggered by endotoxin accumulation. Specifically, the structural integrity of the multi-layered structure plays a vital role in promoting the efficiency of endotoxin removal and the subsequently scavenging of reactive oxygen species. Hemoperfusion simulation experiments demonstrate that the CPG-Ln-MSs could effectively remove endotoxin with a ratio of 92%, and the following oxidative stress state could be well alleviated, as confirmed by the reduced H2O2 and MDA levels in septic blood. Furthermore, endogenous antioxidants could be restored (recover SOD and CAT activity to 96.9 and 10.1 U/mL, respectively) and the red blood cells could be protected from oxidative damage. This study provides a promising therapeutic strategy and guides the design of future for septic blood purification.

Bioinspired Spiky Peroxidase-Mimics for Localized Bacterial Capture and Synergistic Catalytic Sterilization.

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.