Journal
NANO LETTERS
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.3c02414
Keywords
bone metastasis; cancer therapy; ferroptosis; polymer nanoparticles; sonodynamic therapy
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This study presents activatable semiconducting polymer nanoinducers (ASPN(FP)) that amplify oxidative damage through sono-ferroptosis for bone metastasis treatment. ASPN(FP) consist of plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles encapsulated in singlet oxygen (O-1(2))-responsive nanocarriers. Under ultrasound (US) irradiation, ASPN(FP) generate O-1(2) via sonodynamic effect, leading to the destabilization of O-1(2)-responsive nanocarriers and triggering the release of SPNP and Fe3O4 nanoparticles. SPNP decompose polyamines in tumor cells, producing acrolein and hydrogen peroxide (H2O2), with H2O2 facilitating Fenton reaction mediated by Fe3O4 nanoparticles. This induces enhanced ferroptosis and hydroxyl radicals (& BULL;OH) generation, resulting in amplified oxidative damage to inhibit bone metastasis growth and restrict tumor metastasis.
Bone metastases are secondary malignant tumors that commonlyoccurafter the spread of advanced cancer cells. We herein report the activatablesemiconducting polymer nanoinducers (ASPN(FP)) that can amplifyoxidative damage via sono-ferroptosis for bone metastasis treatment.ASPN(FP) are constructed by encapsulating plasma amine oxidase-basedsemiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (O-1(2))-responsive nanocarriers. ASPN(FP) generate O-1(2) under ultrasound (US) irradiation via a sonodynamiceffect to destroy the stability of O-1(2)-responsivenanocarriers, allowing US-triggered releases of SPNP andFe(3)O(4) nanoparticles. SPNP decomposepolyamines in tumor cells to produce acrolein and hydrogen peroxide(H2O2), in which H2O2 promotesFenton reaction mediated by Fe3O4 nanoparticlesfor inducing enhanced ferroptosis and generation of hydroxyl radicals(& BULL;OH). The generated acrolein, O-1(2), and & BULL;OH can simultaneously amplify the oxidative damage. ASPN(FP) thus mediate an amplified sono-ferroptosis effect to inhibitthe growth of bone metastasis and restrict tumor metastasis.
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