通过铁蛋白融合体靶向递送抗菌肽LL-37，可显著提升小鼠脓毒症模型中的抗菌和抗炎疗效。

Abstract

The antimicrobial peptide LL-37 holds considerable therapeutic potential for treating infection and inflammation; however, its clinical application is often limited by poor stability, susceptibility to proteolytic degradation, and insufficient targeting capability. In this study, we engineered a targeted fusion protein (designated as FL) based on ferritin light chain (FTL) by genetically fusing the LL-37 peptide to the C-terminus of FTL, thereby markedly enhancing the structural stability and proteolytic resistance of LL-37. This design further exploits the specific recognition of FTL by scavenger receptor A (SR-A), which is highly expressed on the macrophage surface, to achieve targeted delivery to inflammatory lesions. Both in vitro and in vivo experiments demonstrated that FL not only retained the antimicrobial activity of LL-37, but also exhibited certain anti-inflammatory capacity. In a murine sepsis model, FL exerted superior antibacterial and anti-inflammatory efficacy compared with free LL-37, and partially alleviated structural and functional damage in multiple organs. Moreover, safety evaluations confirmed that FL showed no significant hemolytic activity, immunogenicity or tissue toxicity, indicating good biocompatibility. This study presents a novel protein formulation that integrates enhanced stability, inflammation-targeting capability, and multiple biological activities, thereby providing a promising translational candidate strategy for the precise treatment of infection- and inflammation-related diseases.