Precisely Striking Tumors without Adjacent Normal Tissue Damage via Mitochondria-Templated Accumulation
Precisely Striking Tumors without Adjacent Normal Tissue Damage via Mitochondria-Templated Accumulation
复制标题
通过线粒体模板积累精确打击肿瘤而不损伤邻近正常组织
DOI：
10.1021/acsnano.8b03212
复制
发表时间：
2018-06-01
期刊：
影响因子：
17.1
通讯作者：
Han, Heyou
中科院分区：
文献类型：
--
作者：
Ma, Zhaoyu;Han, Kai;Han, Heyou
邻近正常组织中被忽视的损伤是致命的，特别是在一些特定的肿瘤治疗中，如脑肿瘤，但由于药物的随机扩散和肿瘤的复杂性，它仍然是一个巨大的挑战。在这里，我们表明，在线粒体，粒子间等离子体激元耦合效应激活的纳米事件，高温选择性地打击肿瘤组织，而不损害邻近的正常组织。球形金纳米粒子的靶向部分，三苯基膦，优先积累在肿瘤线粒体内，并达到阈值，激活粒子间的等离子体激元耦合效应，实现选择性光热转换和线粒体功能障碍的肿瘤，而很少高温和线粒体功能障碍观察到在邻近的正常组织。在体研究表明，肿瘤组织中的温度增量与辐射是在邻近的正常组织中的近4倍。这种以亚细胞器为模板的积累策略为高度选择性的肿瘤治疗提供了一种治疗模型，其局部副作用可忽略不计。
Ignored damage in adjacent normal tissue is fatal especially in some specific tumor therapy such as brain tumors, but it remains a great challenge to conquer due to random drug diffusion and tumor complexity. Herein, we show that hyperthermia in mitochondria, an interparticle plasmonic coupling effect activated nanoevent, selectively strikes tumor tissues without damaging adjacent normal tissues. Spherical gold nanoparticles with a mitochondria-targeting moiety, triphenyl phosphonium, preferentially accumulated inside tumor mitochondria and reached the threshold to activate interparticle plasmonic coupling effect among gold nanoparticles, realizing selective light-thermal conversion and mitochondrial dysfunction in tumor, whereas little hyperthermia and mitochondrial dysfunction were observed in adjacent normal tissues. In vivo study revealed that the temperature increment in tumor tissue with irradiation was nearly 4-fold that in adjacent normal tissue. This subcellular organelle-templated accumulation strategy provides a therapeutic model for highly selective tumor therapy with negligible local side effects.