Polylysine-based copolymer self-assemblies featuring acidity-activated structural transformation perceives and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Sepsis is a life-threatening condition with high mortality due to limited effective treatments.
• Current interventions struggle to address the complex pathogenesis involving bacterial infection, inflammation, and oxidative stress.

Purpose of the Study:

• To develop an acidity-activated polylysine (PLL)-based copolymer self-assembly (PPDD) for sepsis treatment.
• To investigate PPDD's efficacy in mitigating bacterial infection, inflammation, and oxidative stress in sepsis.

Main Methods:

• Synthesized PPDD by conjugating PEG-PLL with DCFH-DA.
• Evaluated PPDD's antibacterial, antioxidant, and anti-inflammatory properties in vitro and in vivo.
• Assessed PPDD's structural transformation in acidic environments and its impact on therapeutic effects.
• Monitored sepsis progression and physiological parameters post-treatment.

Main Results:

• PPDD demonstrated rapid ROS neutralization, significant reduction in pro-inflammatory cytokines (TNF-α, IL-6, IL-10), and effective bacterial clearance.
• Day-14 survival rate reached 80% in the PPDD-treated group, compared to 20% in controls.
• Acidity-activated structural reconfiguration of PPDD enhanced ROS scavenging and therapeutic efficacy.
• Biosafety assays showed no hemolysis or organ toxicity.

Conclusions:

• PPDD is a biocompatible, acidity-responsive material with significant potential for sepsis diagnosis and treatment.
• The developed PPDD platform offers a promising therapeutic strategy to improve sepsis patient outcomes.
• Further clinical translation is supported by demonstrated efficacy and safety profiles.