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Dual-Stage-Light-Guided Tumor Inhibition by Mitochondria-Targeted Photodynamic Therapy

机译：线粒体靶向光动力疗法抑制肿瘤的双阶段光导。

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摘要

In this paper, a self-delivery system PpIX-PEG-(KLAKLAK)(2) (designated as PPK) is fabricated to realize mitochondria-targeted photodynamic tumor therapy. It is found that the PPK self-delivery system exhibited high drug loading efficacy as well as novel capacity in generation of intracellular reactive oxygen species (ROS). This study also indicated that the photochemical internalization effect of the photosensitizer protoporphyrin IX (PpIX) under a short time light irradiation improved the cellular internalization of PPK. On the contrary, PPK could target to the subcellular organelle mitochondria due to the presence of proapoptosis (KLAKLAK)(2) peptide. Importantly, the in situ generation of ROS in mitochondria enhanced the photodynamic therapy efficacy under another long time irradiation, leading to significant cell death with decreased mitochondrial membrane potential. Besides, relative high tumor accumulation, minimal systemic cytotoxicity and efficacious long-term tumor inhibition in vivo are also confirmed by using a murine model. All these results demonstrated the self-delivery system PPK with a dual-stage light irradiation strategy is a promising nanoplatform for tumor treatment.
机译：本文构建了一种自传递系统PpIX-PEG-（KLAKLAK）（2）（称为PPK），以实现针对线粒体的光动力肿瘤治疗。发现PPK自递送系统表现出高的药物装载功效以及产生细胞内反应性氧（ROS）的新能力。该研究还表明光敏剂原卟啉IX（PpIX）在短时间光照射下的光化学内在作用改善了PPK的细胞内在化。相反，由于存在促凋亡（KLAKLAK）（2）肽，PPK可能靶向亚细胞器线粒体。重要的是，线粒体中ROS的原位生成在另一种长时间照射下增强了光动力疗法的功效，从而导致了明显的细胞死亡，线粒体膜电位降低。此外，还通过使用鼠模型证实了相对较高的肿瘤积累，最小的全身细胞毒性和有效的体内长期肿瘤抑制作用。所有这些结果表明，具有双阶段光照射策略的自递送系统PPK是用于肿瘤治疗的有前途的纳米平台。

著录项

  • 来源
    《Advanced Functional Materials》 |2015年第20期|2961-2971|共11页
  • 作者

    Han Kai; Lei Qi; Wang Shi-Bo; Hu Jing-Jing; Qiu Wen-Xiu; Zhu Jing-Yi; Yin Wei-Na; Luo Xu; Zhang Xian-Zheng;

  • 作者单位

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China;

    Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China|Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China|Wuhan Univ, Inst Adv Studies, Wuhan 430072, Peoples R China|Hubei Prov Cooperat Innovat Ctr Ind Fermentat, Wuhan 430068, Peoples R China;

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  • 正文语种 eng
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  • 关键词

    mitochondria-target; photochemical internalization; photodynamic therapy; proapoptosis peptide; synergistic therapy;

    机译：线粒体靶标;光化学内在化;光动力疗法;促凋亡肽;协同疗法;

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