Neutrophil-mediated cordycepin-based nanoparticles for targeted treatment of acute lung injury

Abstract

Acute lung injury (ALI) is a life-threatening condition posing significant challenges to healthcare systems. Effective and precise treatment is vital to preventing the progression of ALI. Cordycepin (Cor), an adenosine analogue with potential anti-inflammatory properties, but is limited by enzymatic degradation in vivo. To address these limitations, we investigated the neutrophils involvement in ALI and developed an effective drug delivery platform to enhance the therapeutic potential of Cor. This multifunctional nano-delivery platform, CPPC, incorporates Cor-loaded polydopamine (PDA) nanoparticles modified with anti-CD11b antibodies, utilizing neutrophils for targeted transport to inflamed areas. Our results demonstrate that CPPC is rapidly recruited to inflamed sites during the early stages of ALI. CPPC protect Cor from oxidative degradation during circulation, thereby increasing its concentration in the affected lung tissue. In a murine model of LPS-induced sepsis-related ALI, CPPC significantly reduced systemic levels of pro-inflammatory cytokines and mitigated lung injury. Furthermore, the capacity of CPPC to carry multiple drugs allows for enhanced therapeutic precision. In murine models of Klebsiella pneumoniae and Streptococcus pneumoniae-induced bacterial pneumonia, CPPC was loaded with antibiotics, demonstrating improved delivery efficiency by leveraging neutrophils. This approach significantly reduced bacterial loading, suppressed cytokine storms, and mitigated lung injury, leading to highly effective therapeutic outcomes.