ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy via PI3K/AKT/Mtor Signaling Pathway in M1 Peritoneal Macrophage

Background/Aims: Atherosclerosis is a chronic inflammatory cardiovascular disease.Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors.Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages.In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages.Methods: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ.Intracellular ROS production was assessed by 2′-7′-dichloroflorescein diacetate and flow cytometry.Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence.Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot.Results: Model M1 peritoneal macrophages were established after 24 h induction.Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group.Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT.The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine.Furthermore, ROS generated by UCNPs-