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 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 Fe 3 O 4 nanoparticles into singlet oxygen ( 1 O 2 )-responsive nanocarriers. ASPN FP generate 1 O 2 under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of 1 O 2 -responsive nanocarriers, allowing US-triggered releases of SPN P and Fe 3 O 4 nanoparticles. SPN P decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H 2 O 2 ), in which H 2 O 2 promotes Fenton reaction mediated by Fe 3 O 4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, 1 O 2 , 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.