Xiangjun Chen,* Weiwei Li,* Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong

School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, Yantai, Shandong, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wei Hong; Wenting Li, Email hongwei_sy@bzmc.edu.cn; liwenting1003@163.com

Introduction: Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of P. aeruginosa infection to multiple medications.
Purpose: In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic P. aeruginosa.
Results: As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating P. aeruginosa strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.
Discussion: In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.

Keywords: Pseudomonas aeruginosa, pneumonia, inflammatory responses, β-galactosidase (β-gal)-activated prodrug, amphiphilic Janus nanoparticles