Dexamethasone-loaded ROS-responsive poly(thioketal) nanoparticles suppress inflammation and oxidative stress of acute lung injury

Zihe Zhai; Wei Ouyang; Yuejun Yao; Yuqi Zhang; Haolan Zhang; Feng Xu; Changyou Gao

doi:10.1016/j.bioactmat.2022.01.047

Dexamethasone-loaded ROS-responsive poly(thioketal) nanoparticles suppress inflammation and oxidative stress of acute lung injury

Bioact Mater. 2022 Feb 11:14:430-442. doi: 10.1016/j.bioactmat.2022.01.047. eCollection 2022 Aug.

Authors

Zihe Zhai¹, Wei Ouyang², Yuejun Yao¹, Yuqi Zhang¹, Haolan Zhang¹, Feng Xu², Changyou Gao^{1

3

4}

Affiliations

¹ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
² Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
³ Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China.
⁴ Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

Abstract

Acute lung injury (ALI) is associated with excessive inflammatory response, leading to acute respiratory distress syndrome (ARDS) without timely treatment. A fewer effective drugs are available currently to treat the ALI/ARDS. Herein, a therapeutic nanoplatform with reactive oxygen species (ROS)-responsiveness was developed for the regulation of inflammation. Dexamethasone acetate (Dex) was encapsulated into poly(thioketal) polymers to form polymeric nanoparticles (NPs) (PTKNPs@Dex). The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal) (PPADT) and polythioketal urethane (PTKU), in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site. The PTKNPs@Dex could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly, leading to the decreased ROS level, less generation of pro-inflammatory cytokines, and reduced lung injury and mortality of mice. RNA sequencing (RNA-seq) analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways. These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS.

Keywords: Acute lung injury; Inflammation; Nanoparticles; RNA-Seq; Reactive oxygen species.