Hexahistidine-metal assembly encapsulated fibroblast growth factor 21 for lipopolysaccharide-induced acute lung injury

Lanlan Song; Huihui Ye; Zhanghang Lv; Yichen Liu; Ziyi Lu; Jun Chen; Haofeng Pan; Luqiong Cai; Yuxin Chen; Shiqing Huang; Xingjie Zan; Xiaoying Huang; Chang Yu

doi:10.1016/j.ejpb.2025.114650

Hexahistidine-metal assembly encapsulated fibroblast growth factor 21 for lipopolysaccharide-induced acute lung injury

Eur J Pharm Biopharm. 2025 Jan 25:114650. doi: 10.1016/j.ejpb.2025.114650. Online ahead of print.

Authors

Lanlan Song¹, Huihui Ye¹, Zhanghang Lv¹, Yichen Liu¹, Ziyi Lu¹, Jun Chen¹, Haofeng Pan¹, Luqiong Cai¹, Yuxin Chen², Shiqing Huang², Xingjie Zan³, Xiaoying Huang⁴, Chang Yu⁵

Affiliations

¹ Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
² Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
³ Joint Centre of Translational Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China. Electronic address: zanxj@ucas.ac.cn.
⁴ Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China. Electronic address: huangxiaoying@wzhospital.cn.
⁵ Intervention Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: yuchang@wzhospital.cn.

PMID: 39870250
DOI: 10.1016/j.ejpb.2025.114650

Abstract

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) represents a spectrum of potentially fatal conditions that currently lack effective drug treatment. Recent researches suggest that Fibroblast Growth Factor 21 (FGF21) may protect against ALI/ARDS. However, the clinical use of FGF21 is limited by its rapid degradation, restricted targeting capabilities, and numerous adverse effects. Addressing this challenge, the study employs a pH-responsive nanoparticle delivery system known as Hexahistidine-metal Assembly (HmA) for administering FGF21. The entrapment efficiency (EE%) and loading capacity (LCwt%) of HmA exceed 90 % and 35 %, respectively, while the HmA@FGF21 nanoparticles exhibit an average size of 130 nm, a PDI value of approximately 0.28, and a zeta potential of 24 mV. In animal experiments, HmA@FGF21 administered in lipopolysaccharide (LPS)-induced lung injury significantly exceed those of standalone FGF21, including mitigating the pathological manifestations and reducing the wet/dry ratio, total protein concentration, and overall cell count in BALF of ALI, whether administered via the airway or intravenously. This therapeutic approach therefore shows promise for precise delivery of FGF21 to the lungs to treat ALI, and may offer a novel, and efficient method for delivery of potential pharmacological agents to address other lung diseases.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Drug delivery; Fibroblast Growth Factor 21; HmA@FGF21.