Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis

Abstract

Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPN_FP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPN_FP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPN_P) and Fe₃O₄ nanoparticles into singlet oxygen (¹O₂)-responsive nanocarriers. ASPN_FP generate ¹O₂ under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of ¹O₂-responsive nanocarriers, allowing US-triggered releases of SPN_P and Fe₃O₄ nanoparticles. SPN_P decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H₂O₂), in which H₂O₂ promotes Fenton reaction mediated by Fe₃O₄ nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, ¹O₂, and •OH can simultaneously amplify the oxidative damage. ASPN_FP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.