Rational Design of Cancer-Targeted Selenadiazole Derivative as Efficient Radiosensitizer for Precise Cancer Therapy

Bioconjugate Chemistry
Delong ZengTianfeng Chen

Abstract

Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of targeted therapies for personalized cancer medicine. Herein, cancer targeting RGD peptide has been covalently conjugated to selenadiazole derivative (RGD-SeD) to improve its cancer selectivity. The RGD decoration significantly enhances the anticancer efficacy of RGD-SeD in αVβ3 integrin-overexpressing HepG2 liver cancer cells but not in normal liver cells. Cellular uptake assay and fluorescent imaging confirmed the selectivity of RGD-SeD to integrin-overexpressing cancer cells. RGD-SeD strongly sensitizes HepG2 cells to clinically used X-ray radiotherapy through ROS overproduction, which triggers DNA damage-mediated apoptosis and G2/M cell cycle arrest. This X-ray-responsive DNA damage activates p53 signaling pathways by phosphorylation of ATM/ATR and γ-H2A.X. Furthermore, in a HepG2 nude mice xenograft model, the combined treatment of RGD-SeD and X-ray demonstrates potent in vivo antitumor efficacy via induction of apoptotic cell death but shows no toxicity on the functions of major organs. In summary, this study provides a strategy to design a selenium-based cancer targeting radiosensitizer for preci...Continue Reading

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Citations

Jul 31, 2019·Chemical Communications : Chem Comm·Jinggong LiuTianfeng Chen
Jul 4, 2021·European Journal of Medicinal Chemistry·Hongyan ChuaiMinhang Xin
May 30, 2021·Chemical Biology & Drug Design·Sheng HuangWukun Liu
Feb 21, 2019·Journal of Agricultural and Food Chemistry·Delong ZengTianfeng Chen
Oct 23, 2019·Journal of Medicinal Chemistry·Ana Carolina RuberteDaniel Plano

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