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 (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP 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. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.