Pulmonary Delivery of Theranostic Nanoclusters for Lung Cancer Ferroptosis with Enhanced Chemodynamic/Radiation Synergistic Therapy
Pulmonary Delivery of Theranostic Nanoclusters for Lung Cancer Ferroptosis with Enhanced Chemodynamic/Radiation Synergistic Therapy
复制标题
通过增强化学动力学/放射协同治疗治疗肺癌铁死亡的治疗诊断纳米簇的肺部递送
DOI：
10.1021/acs.nanolett.1c03786
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发表时间：
2022-02-09
期刊：
影响因子：
10.8
通讯作者：
Sun, Xilin
中科院分区：
文献类型：
--
作者：
Li, Yingbo;Yang, Jie;Sun, Xilin
低效的肿瘤聚集和穿透仍然是肺癌治疗效果的主要挑战。局部递送智能纳米簇可以增加药物渗透率，并提供比全身途径更好的抗肿瘤效果。在这里，我们报告了自组装的pH敏感的超顺磁性氧化铁纳米簇(SPIONC)，它可以通过放射治疗和化学动力学治疗增强原位铁下垂和细胞凋亡。在原位肺癌的肺部交付后，SPIONCs分解成更小的纳米颗粒，并在酸性微环境中释放更多的铁离子。在单剂量X射线照射下，内源性超氧化物歧化酶将线粒体产生的超氧阴离子转化为过氧化氢，后者又通过肿瘤内积累的铁离子的芬顿反应产生羟基自由基。最后，辐射和铁离子增强肿瘤脂质过氧化，诱导细胞凋亡和铁下垂。因此，合理设计的肺递送纳米簇为肺癌的非侵入性成像和协同治疗提供了一种有前途的策略。
Inefficient tumor accumulation and penetration remain as the main challenges to therapy efficacy of lung cancer. Local delivery of smart nanoclusters can increase drug penetration and provide superior antitumor effects than systemic routes. Here, we report self-assembled pH-sensitive superparamagnetic iron oxide nanoclusters (SPIONCs) that enhance in situ ferroptosis and apoptosis with radiotherapy and chemodynamic therapy. After pulmonary delivery in orthotopic lung cancer, SPIONCs disintegrate into smaller nano- particles and release more iron ions in an acidic microenvironment. Under single-dose X-ray irradiation, endogenous superoxide dismutase converts superoxide radicals produced by mitochondria to hydrogen peroxide, which in turn generates hydroxyl radicals by the Fenton reaction from iron ions accumulated inside the tumor. Finally, irradiation and iron ions enhance tumor lipid peroxidation and induce cell apoptosis and ferroptosis. Thus, rationally designed pulmonary delivered nanoclusters provide a promising strategy for noninvasive imaging of lung cancer and synergistic therapy.