MR imaging guided iron-based nanoenzyme for synergistic Ferroptosis−Starvation therapy in triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC), as the most aggressive BC, accounts for the leading cause of worldwide women death. Owing to the deficiency of related hormone receptors, the efficacy of hormone therapy on TNBC is significantly confined in clinical treatment. Ferroptosis, a newly emerging antitumor strategy through enhancing iron-dependent lipid peroxides level to induce cancer cell death without the mediation of cell receptors, has been proved to be feasible in various cancer treatments. However, the high glutathione (GSH) level in tumor microenvironment limits the anti-tumor efficacy of ferroptosis. Herein, superparamagnetic iron oxide (SPIO) based nanoenzyme modified with Avastin (Ava) was designed and successfully prepared for synergistic ferroptosis and starvation therapy of TNBC. Through downregulating the GSH and glutathione peroxidase 4 (GPX4), the as-prepared SPIO-based nanoenzyme efficiently improved the ferroptosis efficacy on MDA-MB-231 ​cells. Besides that, the integration of starvation therapy based on Ava modification greatly decreased the expression of CD31, resulted to a nutrient-deprived status and thus significantly enhanced ferroptosis efficacy in a synergistic manner. Concluded from the antitumor investigation on an MDA-MB-231 ​cells xenograft mice model, the systemic administration of this nanoenzyme effectively inhibited the tumor growth and successfully enhanced the mice survival rate. Overall, we believe this biocompatible synergistic ferroptosis-starvation nanoenzyme may provide a refreshing scope to the clinical treatment of TNBC.

Keywords

• Nanoenzyme
• Triple negative breast cancer
• Ferroptosis
• MR imaging