Precise anti-inflammatory nano-contrast agents to treat Hashimoto thyroiditis by sustainably targeting HLA-DR

Abstract

Abstract According to previous reports, in vivo precision treatment using nanocarrier systems has proven effective in a variety of diseases. This work aimed to synthesize controlled nano-ultrasound contrast agents loaded with small interfering ribonucleic acid (siRNA) and drugs to target thyroid tissue and to evaluate this non-invasive method’s therapeutic effect on Hashimoto thyroiditis (HT) and the underlying mechanism thereof. In this study, we used high-biocompatibility anti-inflammatory nano-contrast agents (AINAs) with an erythrocyte membrane as the shell; the surface of this membrane was grafted with rapamycin. Its core included mesoporous-silica nanoparticles loaded with class II transactivator (CIITA)–siRNA and Trans-Activator of Transcription (TAT) transduction peptide. As seen under light and electron microscopes, each AINA was a approximately 255nm elliptical nanodroplet. AINAs could achieve long-lasting circulation in the bloodstream and targeted release of CIITA-siRNA and rapamycin into thyroid cells and the thyroid tissue microenvironment, respectively, with the assistance of the ultrasound-targeted microbubble destruction effect and TAT transduction peptide. AINAs could also be clearly visualized on contrast-enhanced ultrasound. They worked against multiple mechanisms to alleviate inflammatory trauma, including downregulation of HLA-DR expression, inhibition of antigen presentation and T-cell activation, reactive oxygen species levels, and anti-apoptosis of thyroid cells. In summary, our results showed that AINAs are a safe, effective treatment for HT.