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

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) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPN are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPN) and FeO nanoparticles into singlet oxygen (O)-responsive nanocarriers. ASPN generate O under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of O-responsive nanocarriers, allowing US-triggered releases of SPN and FeO nanoparticles. SPN decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (HO), in which HO promotes Fenton reaction mediated by FeO nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, O, and •OH can simultaneously amplify the oxidative damage. ASPN thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.