Upconversion nanoparticle-mediated photodynamic therapy induces autophagy and cholesterol efflux of macrophage-derived foam cells via ROS generation

Abstract

Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect. First, we found that PDT notably enhanced the cholesterol efflux and the induction of autophagy in both THP-1 and peritoneal macrophage-derived foam cells. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA significantly attenuated PDT-induced autophagy, which subsequently suppressed the ABCA1-mediated cholesterol efflux. Furthermore, the reactive oxygen species (ROS) produced by PDT were responsible for the induction of autophagy, which could be blocked by the ROS inhibitor N-acetyl cysteine (NAC). NAC also reversed the PDT-induced suppression of p-mTOR and p-Akt. Therefore, our findings demonstrate that PDT promotes cholesterol efflux by inducing autophagy, and the autophagy was mediated in part through the ROS/PI3K/Akt/mTOR signaling pathway in THP-1 and peritoneal macrophage-derived foam cells.

Photodynamic treatment with anionic nanoclays containing curcumin on human triple‐negative breast cancer cells: Cellular and biochemical studies

“…The data are shown as the mean ± standard deviation of three experiments. 49 The ROS production detection results show that in 25 µg/mL of curcumin-LDH and then PDT the ROS production is higher than control even than 100 µg/mL. In IC 50 there are not any autophagic vacuoles may be it is due to another cell death mechanism under PDT.…”

Targeting the ROS/PI3K/AKT/HIF‐1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2‐Deoxy‐d‐glucose

“…45 It is generally accepted that ROS are tumour suppressors that are implicated in tumorigenesis, progression and survival phenotypes. 47,48 ROS is a double-edged sword and the influence of ROS within cancer cells, whether they are favourable or harmful, may depend on several factors, such as cell type, stimulus, duration, specificity and levels of ROS. 47,48 ROS is a double-edged sword and the influence of ROS within cancer cells, whether they are favourable or harmful, may depend on several factors, such as cell type, stimulus, duration, specificity and levels of ROS.…”

“…It should be noted that a few studies have shown that AKT was also found to be down-regulated by ROS in cancer cells. 47,48 ROS is a double-edged sword and the influence of ROS within cancer cells, whether they are favourable or harmful, may depend on several factors, such as cell type, stimulus, duration, specificity and levels of ROS.…”

ATP‑binding cassette transporter A1: A promising therapy target for prostate cancer (Review)

“…Of note, all these lipoproteins increase autophagic flux in macrophages, and autophagy depletion in these cells results in diminished cholesterol efflux to apoA-I. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA were found to significantly attenuate autophagy, subsequently suppressing the ABCA1-mediated cholesterol efflux (48). Biochemical studies have demonstrated that the accumulation of cholesterol esters in prostate cancer cells is the result of loss of the tumor suppressor PTEN and activation of the PI3K/Akt pathway.…”