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

• Published in: Bioactive materials 2022-08, Vol.14, p.430-442
• Main Authors: Zhai, Zihe, Ouyang, Wei, Yao, Yuejun, Zhang, Yuqi, Zhang, Haolan, Xu, Feng, Gao, Changyou
• Format: Article
• Language: English
• Subjects: Acute lung injury; Inflammation; Nanoparticles; Reactive oxygen species; RNA-Seq
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.01.047

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. A therapeutic nanoplatform composed of low Mw of poly(1,4-phenyleneacetonedimethylene thioketal) and high Mw of polythioketal urethane was developed with the feature of ROS scavenging and anti-inflammation. The dexamethasone acetate-loaded NPs significantly decreased lung inflammation, and reduced lung injury and mortality in vivo. [Display omitted] •A therapeutic nanoplatform with ROS-responsiveness was developed for the regulation of inflammation.•NPs composed of low Mw of PPADT and high Mw of PTKU were loaded with dexamethasone to obtain a self-adaptive system.•The Dex-loaded NPs significantly decreased lung inflammation, and reduced lung injury and mortality in vivo.