Aggregation-Induced Emission Photosensitizer-Armored Magnetic Nanoparticles for Sepsis Treatment: Combating Multidrug-Resistant Bacteria and Alleviating Inflammation

Sepsis, a life-threatening condition stemming from an uncontrolled host immune response to bacterial infections, continues to impose a significant global burden with high morbidity and mortality. Addressing the challenges posed by antimicrobial resistance and uncontrollable inflammation remains a challenge in sepsis treatment. Moreover, traditional antibacterial materials have low bacterial trapping efficiency and inevitable prolonged circulation within the bloodstream, resulting in suboptimal antibacterial effects, metabolic complications, and undesirable side effects. In this study, an innovative solution is introduced through the development of Fe3O4@SH@TBTCP-PMB, an aggregation-induced emission (AIE) photosensitizer (PS)-armored magnetic nanoparticles (NPs). It has high reactive oxygen species (ROS) generation efficiency and an exceptional ability to capture Gram-positive bacteria with over 80% enrichment efficiency within just 1 h, even at low bacterial concentrations. Under white light illumination, 100 mu g mL-1 of Fe3O4@SH@TBTCP-PMB effectively eliminated more than 99.9% of methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, its magnetic separation properties efficiently prevent systemic blood circulation and associated side effects. Most importantly, Fe3O4@SH@TBTCP-PMB demonstrates superior anti-inflammatory effects by regulating cytokines, reducing adhesion molecule expression, and managing oxidative stress levels. This multifunctional approach significantly enhances sepsis survival rates, offering a promising strategy for combating multidrug-resistant (MDR) bacterial infections in sepsis patients while addressing inflammation-related complications. An aggregation-induced emission photosensitizer-armored magnetic nanoparticle, Fe3O4@SH@TBTCP-PMB, that combines high ROS generation efficiency and magnetic trapping and separation character to circumvent the potential toxic side effects associated with prolonged blood circulation and metabolic challenges. It efficiently traps Gram-positive bacteria, eliminates multidrug-resistant bacteria, attenuates the inflammatory response, and restores the innate immune defense system to conquer sepsis in mouse model.image