声动力铁死亡型纳米引发剂通过激活半导体聚合物放大氧化损伤用于协同治疗骨转移
Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis.
机构信息
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
出版信息
Nano Lett. 2023 Aug 23;23(16):7699-7708. doi: 10.1021/acs.nanolett.3c02414. Epub 2023 Aug 11.
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.
骨转移是晚期癌细胞扩散后常见的继发性恶性肿瘤。我们在此报告了可激活的半导体聚合物纳米敏化剂（ASPN），它可以通过声铁死亡来放大氧化损伤，从而治疗骨转移。ASPN 通过将基于血浆胺氧化酶的半导体聚合物纳米颗粒（SPN）和 FeO 纳米颗粒封装到单重态氧（O）响应性纳米载体中构建而成。ASPN 在超声（US）照射下通过声动力学效应产生 O，破坏 O 响应性纳米载体的稳定性，从而实现 US 触发的 SPN 和 FeO 纳米颗粒的释放。SPN 分解肿瘤细胞中的多胺产生丙烯醛和过氧化氢（HO），其中 HO 通过 FeO 纳米颗粒介导的芬顿反应促进诱导增强的铁死亡和羟基自由基（•OH）的产生。生成的丙烯醛、O 和 •OH 可以同时放大氧化损伤。因此，ASPN 介导了放大的声铁死亡效应，抑制了骨转移的生长并限制了肿瘤转移。
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