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Dual‐Stage‐Light‐Guided Tumor Inhibition by Mitochondria‐Targeted Photodynamic Therapy
Author(s) -
Han Kai,
Lei Qi,
Wang ShiBo,
Hu JingJing,
Qiu WenXiu,
Zhu JingYi,
Yin WeiNa,
Luo Xu,
Zhang XianZheng
Publication year - 2015
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201500590
Subject(s) - photodynamic therapy , internalization , photosensitizer , protoporphyrin ix , mitochondrion , reactive oxygen species , cytotoxicity , in vivo , cancer research , intracellular , programmed cell death , biophysics , materials science , cell , microbiology and biotechnology , chemistry , in vitro , apoptosis , biology , biochemistry , photochemistry , organic chemistry
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.