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

Zhang, Yijing; Zhang, Qin; Wang, Fengshuo; Li, Meng; Shi, Xiangyang; Li, Jingchao · Nano Lett · 2023

basic_science · Level V

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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<sub>FP</sub>) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPN<sub>FP</sub> are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPN<sub>P</sub>) and Fe<sub>3</sub>O<sub>4</sub> nanoparticles into singlet oxygen (<sup>1</sup>O<sub>2</sub>)-responsive nanocarriers. ASPN<sub>FP</sub> generate <sup>1</sup>O<sub>2</sub> under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of <sup>1</sup>O<sub>2</sub>-responsive nanocarriers, allowing US-triggered releases of SPN<sub>P</sub> and Fe<sub>3</sub>O<sub>4</sub> nanoparticles. SPN<sub>P</sub> decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), in which H<sub>2</sub>O<sub>2</sub> promotes Fenton reaction mediated by Fe<sub>3</sub>O<sub>4</sub> nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, <sup>1</sup>O<sub>2</sub>, and •OH can simultaneously amplify the oxidative damage. ASPN<sub>FP</sub> thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.

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