摘要
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.
基金
financially supported by the Natural Science Foundation of Zhejiang Province(LD21E030001)
National Natural Science Foundation of China(51873188,81770008)
the Fundamental Research Funds for the Central Universities of China(2020XZZX004-01).
