siRNA@superparamagnetic iron oxide nanoparticles attenuate physiological toxicity of DEHP by suppressing autophagy pathway activities in Caenorhabditis elegans

Abstract

Bis(2-ethylhexyl)ortho-phthalate (DEHP) is a widely used plasticizer in polyvinyl chloride materials. Considering its widespread application, it has become a major environmental pollutant and can cause endocrine, reproductive system, and gastrointestinal disorders. Herein we aimed to elucidate the mechanisms via which DEHP causes cytotoxicity in Caenorhabditis elegans and assess whether siRNA@superparamagnetic iron oxide nanoparticles (SPIONs) can attenuate this effect. On exposing C. elegans to 10 μM DEHP, its physiological functions and gene expression levels were markedly affected. RNA-seq and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that DEHP exposure significantly activated the autophagy-animal signal transduction pathway in the somatic cells of C. elegans. Subsequently, the surface of SPIONs was loaded with siRNAs and transfected into C. elegans. Transmission electron microscopy showed that SPIONs could smoothly enter the somatic cells of C. elegans. Further, qPCR showed that the expression levels of autophagy pathway-related genes, namely Atg-2, Epg-9, Atg-18, Bec-1, and Atg-16.2, in the siRNA@SPION intervention group were significantly lower than those in the control group. Biochemical and physiological test results suggested that siRNA@SPION complexes attenuated DEHP-induced physiological toxicity and oxidative stress damage in C. elegans. Collectively, our findings indicated that DEHP markedly affects the physiological activity of C. elegans, induces changes in gene expression levels, and activates the autophagy signal transduction pathway and that siRNA@SPION complexes suppress such toxic effects by silencing the expression of genes involved in the autophagy signal transduction pathway.

Keywords

• Autophagy
• Environmental pollution
• Oxidative stress damage
• SiRNA
• Signal transduction
• Nanoparticles