Multifunctional Engineered Nano-selenium Biomimetic bioparticles Unleash Potent Trained Immunity via Metabolic and Epigenetic Reprogramming for Superior Antimicrobial Defense and Antigen Delivery
Description
Here, we developed a multifunctional biomimetic bioparticles (SeBLP) based on a microbial strategy, featuring a rapid and simple preparation process, excellent biocompatibility, and cost-effectiveness. SeBLP exhibits potent antioxidant, anti-infective, and antigen delivery capabilities. We found that SeBLP exhibits excellent capabilities in scavenging DPPH and ABTS free radicals, showing antioxidant enzyme activity, and significantly inhibiting the growth of various bacteria in vitro. Subsequently, in vivo, SeBLP demonstrates rapid and broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. Importantly, SeBLP induces trained immunity by reprogramming macrophage metabolism and epigenetics via the GSH–ROS–mTOR/NF-κB pathway, while maintaining redox homeostasis and inflammatory balance. Furthermore, a single immunization with SeBLP conjugated to a Staphylococcus aureus model antigen significantly enhances immune protection against MRSA and elicits a balanced Th response. Our study demonstrates that SeBLP is a multifunctional bioparticles integrating biocompatibility, antimicrobial activity, antioxidant capacity, and antigen delivery, while inducing trained immunity to coordinate metabolic reprogramming and inflammation balance, resulting in rapid, broad-spectrum anti-infection and immune-enhancing effects. The findings of this study provide novel insights into the development of advanced multifunctional materials that utilize trained immunity to enhance immune resistance and prevent infectious diseases.