Dual‐Stage‐Light‐Guided Tumor Inhibition by Mitochondria‐Targeted Photodynamic Therapy. (8th April 2015)

• Record Type: Journal Article
• Authors: Han, Kai; Lei, Qi; Wang, Shi‐Bo; Hu, Jing‐Jing; Qiu, Wen‐Xiu; Zhu, Jing‐Yi; Yin, Wei‐Na; Luo, Xu; Zhang, Xian‐Zheng
• Is Part Of: Advanced functional materials. Volume 25:Number 20(2015)
• Page Start: 2961
• Page End: 2971
• Publication Date: 2015-04-08
• Subjects: mitochondria‐target -- photochemical internalization -- photodynamic therapy -- proapoptosis peptide -- synergistic therapy; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201500590
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract : 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. Abstract : A mitochondria‐targeted self‐delivery system is developed for optical‐imaging‐guided photodynamic tumor therapy. A dual‐stage light irradiation strategy is used to optimize the synergistic effect between photosensitizer and (KLAKLAK)2, and significant efficacious tumor inhibition is observed both in vitro and in vivo.