Time and Space Dual-Blockade Strategy for Highly Invasive Nature of Triple-Negative Breast Cancer in Enhanced Sonodynamic Therapy Based on Fe-MOF Nanoplatforms.

Abstract

Triple-negative breast cancer (TNBC), due to its high malignant degree and strong invasion ability, leads to poor prognosis and easy recurrence, so effectively curbing the invasion of TNBC is the key to obtaining the ideal therapeutic effect. Herein, a therapeutic strategy is developed that curbs high invasions of TNBC by inhibiting cell physiological activity and disrupting tumor cell structural function to achieve the time and space dual-blockade. The time blockade is caused by the breakthrough of the tumor-reducing blockade based on the ferroptosis process and the oxidation-toxic free radicals generated by enhanced sonodynamic therapy (SDT). Meanwhile, alkyl radicals from 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) and 1 O2 attacked the organelles of tumor cells under ultrasound (US), reducing the physiological activity of the cells. The attack of free radicals on the cytoskeleton, especially on the proteins of F-actin and its assembly pathway, achieves precise space blockade of TNBC. The damage to the cytoskeleton and the suppression of the repair process leads to a significant decline in the ability of tumor cells to metastasize and invade other organs. In summary, the FTM@AM nanoplatforms have a highly effective killing and invasion inhibition effect on invasive TNBC mediated by ultrasound, showcasing promising clinical transformation potential.