Mesopore-encaged active MnOx in nano-silica selectively suppresses lung cancer cells by inducing autophagy

Autophagy induced by nanomaterials is one of the intracellular catabolic pathways that degrade and recycle the biomacromolecules and damaged organelles in cells and has emerged as a very promising pharmacological target critical to future drug development and anti-cancer therapy. Herein, we developed mesopore-encaged highly-dispersed active cluster-like MnOx in nanosilica entitled MnO-MS, with a size of around 130 nm. Our studies show that MnO-MS could not only obviously induce autophagy in both stable GFP-LC3 HeLa cells and GFP-LC3-mCherry HeLa cells but also could selectively inhibit lung cancer A549 cell growth at 11.19 mu g mL(-1) (IC50) while exhibiting little cytotoxicity in normal cells. Encouraged by these interesting results, a further mechanistic study reveals that reactive oxygen species (ROS) were excited by the active MnOx in nanosilica, leading to the disruption of mitochondrial membrane potential (MMP), enhancement of ATG5A/ATG16L/ATG4B/Beclin1, and finally, inhibition of the mTOR signaling pathways. Collectively, these findings indicate that MnO-MS-induced cell death via autophagy pathways in cancer cells. Furthermore, MnO-MS significantly inhibited tumor growth with minimal side effects in vivo, and it is envisioned that MnO-MS can be further developed as a potential autophagy inducer for the treatment of lung cancers.

Automated summary

Autophagy induced by nanomaterials has emerged as a promising pharmacological target for drug development and anti-cancer therapy. The researchers developed a highly-dispersed active cluster-like MnOx in nanosilica named MnO-MS, which could induce autophagy and selectively inhibit lung cancer cell growth with low cytotoxicity in normal cells. Mechanistic studies revealed that the active MnOx generated reactive oxygen species, leading to disruption of mitochondrial membrane potential and inhibition of the mTOR signaling pathways, ultimately resulting in cancer cell death. In vivo studies demonstrated that MnO-MS effectively inhibited tumor growth with minimal side effects, suggesting its potential as an autophagy inducer for lung cancer treatment.