Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer
Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer
复制标题
线粒体靶向磁性复合纳米粒子用于增强癌症光疗
DOI：
10.1002/smll.201601094
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发表时间：
2016-09-07
期刊：
影响因子：
13.3
通讯作者：
Yang, Wuli
中科院分区：
文献类型：
--
作者：
Guo, Ranran;Peng, Haibao;Yang, Wuli
光热疗法（PTT）和光动力疗法（PDT）是当今有前景的癌症治疗方式，但高激光功率密度需求和低肿瘤积累是极大限制其发展的关键障碍。在此，报道了用于双模式 PTT 和 PDT 的磁性复合纳米颗粒，通过线粒体靶向实现了增强癌症治疗效果。将PTT剂和光敏剂结合在一起，复合纳米颗粒能够在近红外（NIR）激光照射下同时产生热量和活性氧（ROS）。经过靶向配体的表面修饰后，复合纳米颗粒可以选择性地递送至线粒体，从而放大热疗和细胞毒性ROS诱导的癌细胞凋亡。这样，在低激光功率密度下，与使用缺少线粒体靶向单元的相同纳米颗粒处理相比，利用复合纳米颗粒实现了更好的光治疗效果和更高的细胞毒性。在近红外荧光成像和磁共振成像的指导下，这些结果在人源化正交异性肺癌模型中得到证实。复合纳米粒子表现出高肿瘤积累和出色的肿瘤消退，并且在近红外激光照射下副作用最小。因此，靶向线粒体的复合纳米粒子有望成为肿瘤治疗中有效的光疗平台。
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.