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4-Hydroxyl-oxoisoaporphine, one small molecule as theranostic agent for simultaneous fluorescence imaging and photodynamic therapy as type II photosensitizer

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Abstract

Oxoisoaporphine (OA) is a plant phototoxin isolated from Menispermaceae, however, its weak fluorescence and low water solubility impede it for theranostics. We developed here 4-hydroxyl-oxoisoaporphine (OHOA), which has good singlet oxygen-generating ability (0.06), strong fluorescence (0.72) and improved water solubility. OHOA displays excellent fluorescence for cell imaging and exhibits light-induced cytotoxicity against cancer cell. In vitro model of human cervical carcinoma (HeLa) cell proved that singlet oxygen generated by OHOA triggered photosensitized oxidation reactions and exert toxic effect on tumor cells. The MTT assay using HeLa cells verified the low cytotoxicity of OHOA in the dark and high phototoxicity. Confocal experiment indicates that OHOA mainly distributes in mitochondria and western blotting demonstrated that OHOA induces cell apoptosis via the mitochondrial pathway in the presence of light. Our molecule provides an alternative choice as a theranostic agent against cancer cells which usually are in conflict with each other for most traditional theranostic agents.

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All data generated or used during the study appear in the submitted article and supplementary information. The data used to support the findings of this study are also available from the corresponding author upon request.

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Acknowledgements

This work was financial supported by National Key Research and Development Program of China (2018YFD0200100), National Natural Science Foundation of China (No. 21877039), Science and Technology Commission of Shanghai Municipality (16391902300) and Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00037).

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Authors and Affiliations

  1. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China

    Qi Xu, Yunfan Ji, Meijun Chen & Xusheng Shao

  2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Xusheng Shao

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  1. Qi Xu
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  2. Yunfan Ji
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  3. Meijun Chen
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  4. Xusheng Shao
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XS designed experiments; QX and YJ carried out experiments; MC analyzed experimental results. QX and XS wrote the manuscript.

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Correspondence to Xusheng Shao.

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Xu, Q., Ji, Y., Chen, M. et al. 4-Hydroxyl-oxoisoaporphine, one small molecule as theranostic agent for simultaneous fluorescence imaging and photodynamic therapy as type II photosensitizer. Photochem Photobiol Sci 20, 501–512 (2021). https://doi.org/10.1007/s43630-021-00030-0

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