Cell-penetrating riboflavin conjugate for antitumor photodynamic therapy

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 Arg(8), (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 Args-RF, (Cha-Arg)(3)-RF and TPP-RF, respectively. Compared with TPP-RF and Args-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. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

By preparing three RF conjugates using cell-penetrating peptides and small molecule delivery compounds, this study increased the cellular uptake of RF and found that one of the conjugates ((Cha-Arg)(3)-RF) exhibited better cell internalization and stronger cytotoxicity against HeLa cells upon exposure to blue light.