Residual Ammonium Persulfate in Nanoparticles Has Cytotoxic Effects on Cells through Epithelial-Mesenchymal Transition

Ammonium persulfate (APS), a low molecular weight chemical compound with strong oxidizing properties, should to be totally removed during preparation of nanomaterials due to its cytotoxicity. APS exerts its oxidative stress effects mainly on cell membrane, but its intracellular influence remains unclear. Here, we designed a facile negatively-charged carboxylic gelatin-methyacrylate (carbox-GelMA) nanoparticle (NP) as a cargo-carrier through the catalytic and oxidizing action of APS in W/O system. The formed APS-loaded carbox-GelMA NPs (APS/NPs) were transported into the lysosome in MCF-7 breast cancer cells. The intracellular APS/NPs produced a high level of oxidative stress in lysosome and induced epithelial-mesenchymal transition (EMT). Consequently, the MCF-7 cells challenged with APS/NPs had a strong metastatic and invasive capability in vitro and in vivo. This study highlights that a facile APS-loaded nanocarrier has cyctotoxicity on cells through EMT. Unexpectedly, we found a novel pathway inducing EMT via lysosomal oxidative stress.