Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS). Moreover, the dual-targeting property facilitated the effective subcellular localization of photosensitizer protoporphyrin IX (PpIX) to generate ROS in situ for enhanced photodynamic therapy (PDT). Notably, plasma membrane-targeted PDT would enhance the membrane permeability to improve the cellular delivery of M-ChiP, and even directly disrupt the cell membrane to induce cell necrosis. Additionally, mitochondria-targeted PDT would decrease mitochondrial membrane potential and significantly promote the cell apoptosis. Both in vitro and in vivo investigations indicated that this combinatorial PDT in mitochondria and plasma membrane could achieve the therapeutic effect maximization with reduced side effects. The single-agent self-delivery system with dual-targeting strategy was demonstrated to be a promising nanoplatform for synergistic tumor therapy.

中文翻译：

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用于单药协同光动力疗法的线粒体和质膜双靶向嵌合肽。

线粒体和细胞膜在维持细胞活性和稳定性中起重要作用。在这里，开发了一种基于单药自递送嵌合肽的纳米颗粒（称为M-ChiP）用于线粒体和质膜双靶向光动力肿瘤治疗。在没有其他载体的情况下，M-ChiP具有高载药量以及产生活性氧（ROS）的出色能力。此外，双重靶向特性促进了光敏剂原卟啉IX（PpIX）的有效亚细胞定位，从而在原位生成ROS，从而增强了光动力疗法（PDT）。值得注意的是，靶向质膜的PDT将增强膜通透性，从而改善M-ChiP的细胞传递，甚至直接破坏细胞膜以诱导细胞坏死。此外，线粒体靶向的PDT将降低线粒体膜电位并显着促进细胞凋亡。体外和体内研究均表明，线粒体和质膜中的这种组合PDT可以实现最大程度的治疗效果，同时减少副作用。具有双重靶向策略的单剂自我递送系统被证明是用于协同肿瘤治疗的有前途的纳米平台。