Citation: Chunlei Wu, Yanyan Li, Zhehong Cheng, Pengxin Wang, Zhilong Ma, Ke Liu, Yulian Cheng, Yimin Zhou, Xian Lin, Ximing Shao, Yong Yang, Hongchang Li, Lijing Fang. Cell-penetrating riboflavin conjugate for antitumor photodynamic therapy[J]. Chinese Chemical Letters, ;2022, 33(9): 4339-4344. doi: 10.1016/j.cclet.2022.01.036 shu

Cell-penetrating riboflavin conjugate for antitumor photodynamic therapy

Chunlei Wu ^{a, 1} ,
Yanyan Li ^{a, b, 1} ,
Zhehong Cheng ^{a, 1} ,
Pengxin Wang ^a ,
Zhilong Ma ^a ,
Ke Liu ^a ,
Yulian Cheng ^a ,
Yimin Zhou ^a ,
Xian Lin ^a ,
Ximing Shao ^a ,
Yong Yang ^{c, *,} ,
Hongchang Li ^{a, b, *,} ,
Lijing Fang ^{a, b, *,}

a.
Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
b.
University of Chinese Academy of Sciences, Beijing 100049, China
c.
Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China

yangy9@sustech.edu.cn

hc.li@siat.ac.cn

lj.fang@siat.ac.cn

Received Date: 14 October 2021
Revised Date: 13 January 2022
Accepted Date: 14 January 2022
Available Online: 19 January 2022

Figures(7)

Riboflavin (RF, vitamin B2) is an essential vitamin and has been considered as a promising natural photosensitizer for photodynamic therapy (PDT). However, further exploration of RF in antitumor application was limited by its poor cellular uptake. In this study, using cell-penetrating peptides Arg₈, (Cha-Arg)₃ and small molecule triphenylphosphine (TPP) as delivery compounds, three RF conjugates were prepared to increase the accumulation of RF in cells, termed as Arg₈-RF, (Cha-Arg)₃-RF and TPP-RF, respectively. Compared with TPP-RF and Arg₈-RF, (Cha-Arg)₃-RF exhibited better cell internalization and stronger cytotoxicity against HeLa cells upon exposure to blue light. Further researches proved that (Cha-Arg)₃-RF generated reactive oxygen species (ROS) under irradiation, which could indiscriminately destroy endogenous proteins and mitochondria, ultimately inducing cell death. This work provides a new approach to explore RF as a natural photosensitizer for antitumor photodynamic therapy.
- Riboflavin,
- Antitumor,
- Photodynamic therapy,
- Cell-penetrating peptides
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