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Hypoxia-activated NIR photosensitizer anchoring in the mitochondria for photodynamic therapy

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Abstract

Photodynamic therapy is considered as a promising treatment for cancer, but still faces several challenges. The hypoxic environment in solid tumors, imprecise tumor recognition and the lack of selectivity between normal and cancer cells extremely hinder the applications of photodynamic therapy in clinics. Moreover, the “always on” property of photosensitizers also increases the toxicity to normal tissues when exposed to light irradiation. In this study, a hypoxia-activated NIR photosensitizer ICy-N was synthesized and successfully applied for in vivo cancer treatment. ICy-N is in the inactivated state with low fluorescence whereas its NIR emission (λem = 716 nm) was induced via reduction caused by nitroreductase at the tumor site. In addition, the reduced product ICy-OH was specially located in the mitochondria and demonstrated a high singlet oxygen production under 660 nm light irradiation, which efficiently induced cell apoptosis (IC50 = 0.63 μM). The in vivo studies carried out in Balb/c mice indicated that ICy-N was suitable for precise tumor hypoxia imaging and can work as an efficient photosensitizer for restraining tumor growth through the PDT process.

Graphical abstract: Hypoxia-activated NIR photosensitizer anchoring in the mitochondria for photodynamic therapy

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Publication details

The article was received on 08 Jul 2019, accepted on 01 Oct 2019 and first published on 02 Oct 2019


Article type: Edge Article
DOI: 10.1039/C9SC03355F
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Hypoxia-activated NIR photosensitizer anchoring in the mitochondria for photodynamic therapy

    F. Xu, H. Li, Q. Yao, H. Ge, J. Fan, W. Sun, J. Wang and X. Peng, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC03355F

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