School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA.
Nanoscale. 2017 Oct 26;9(41):15813-15824. doi: 10.1039/c7nr04881e.
In the conventional non-invasive cancer treatments, such as photodynamic therapy (PDT) and photothermal therapy (PTT), light irradiation is precisely focused on tumors to induce apoptosis via the generation of reactive oxygen species (ROS) or localized heating. However, overconsumption of oxygen and restricted diffusion distance of ROS limit the therapeutic effects on hypoxic tumors. Herein, we developed a platform for the rapid uptake of multifunctionalized Au@Pt nanoparticles (NPs) by mitochondria in cancer cells. The mesoporous Au@Pt nanoparticles were labeled with a cell-targeting ligand (folic acid), a mitochondria-targeting group (triphenylphosphine (TPP)), and a photosensitizer (Ce6). This led to significant improvement of the PDT efficacy due to an enhanced cellular uptake, an effective mitochondrial ROS burst, and a rapid intelligent release of oxygen. Moreover, Au@Pt NPs can convert laser radiation into heat, resulting in thermally induced cell damage. This nanosystem could be used as a dual-mode phototherapeutic agent for enhanced cancer therapy and molecular targets associated with disease progression. We achieved a mitochondria-targeted multifunctional therapy strategy (a combination of PDT and PTT) to substantially improve the therapeutic efficiency.
在传统的非侵入性癌症治疗方法中,如光动力疗法(PDT)和光热疗法(PTT),通过产生活性氧(ROS)或局部加热,精确地将光照射在肿瘤上以诱导细胞凋亡。然而,氧气的过度消耗和 ROS 的扩散距离限制了对缺氧肿瘤的治疗效果。在此,我们开发了一种平台,用于癌症细胞中的线粒体快速摄取多功能化的 Au@Pt 纳米颗粒(NPs)。介孔 Au@Pt 纳米颗粒被标记上细胞靶向配体(叶酸)、线粒体靶向基团(三苯基膦(TPP))和光敏剂(Ce6)。这导致 PDT 疗效显著提高,原因是细胞摄取增强、有效的线粒体 ROS 爆发以及氧气的快速智能释放。此外,Au@Pt NPs 可以将激光辐射转化为热能,导致热诱导的细胞损伤。该纳米系统可用作双重模式光疗剂,用于增强癌症治疗和与疾病进展相关的分子靶标。我们实现了一种线粒体靶向的多功能治疗策略(PDT 和 PTT 的组合),大大提高了治疗效率。