Synergistic anti-oxidant and anti-inflammatory effects of ceria/resatorvid co-decorated nanoparticles for acute lung injury therapy

Author:

Wu Yue,Zhang Yawen,Tang Xuanyu,Ye Shuhui,Shao Jingjing,Tu Linglan,Pan Junzhi,Chen Lingfeng,Liang Guang,Yin Lina

Abstract

Abstract Background Acute lung injury (ALI) is a critical inflammatory response syndrome that rapidly develops into acute respiratory distress syndrome (ARDS). Currently, no effective therapeutic modalities are available for patients with ALI/ARDS. According to recent studies, inhibiting both the release of pro-inflammatory cytokines and the formation of reactive oxygen species (ROS) as early as possible may be a promising therapy for ALI. Results In this study, a ROS-responsive nano-delivery system based on oxidation-sensitive chitosan (Ox-CS) was fabricated for the simultaneous delivery of Ce NPs and RT. The in vitro experiments have shown that the Ox-CS/Ceria-Resatorvid nanoparticles (Ox-CS/CeRT NPs) were rapidly and efficiently internalised by inflammatory endothelial cells. Biological evaluations validated the significant attenuation of ROS-induced oxidative stress and cell apoptosis by Ox-CS/CeRT NPs, while maintaining mitochondrial function. Additionally, Ox-CS/CeRT NPs effectively inhibited the release of pro-inflammatory factors. After intraperitoneal (i.p.) administration, Ox-CS/CeRT NPs passively targeted the lungs of LPS-induced inflamed mice and released the drug activated by the high ROS levels in inflammatory tissues. Finally, Ox-CS/CeRT NPs significantly alleviated LPS-induced lung injury through inhibiting both oxidative stress and pro-inflammatory cytokine expression. Conclusions The created Ox-CS/CeRT NPs could act as a prospective nano-delivery system for a combination of anti-inflammatory and anti-oxidant therapy of ALI. Graphical Abstract

Funder

the Natural Science Foundation of Zhejiang Province, China

the Medical and Health Technology Project of Zhejiang Province, China

Basic Scientific Research Project of Hangzhou Medical College

the Special Project of Zhejiang Academy of Medical Sciences

Publisher

Springer Science and Business Media LLC

Subject

Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering

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