Details

Autor(en) / Beteiligte

• Huang, Kunshan
• Xie, Song
• Wang, Weijun
• Wu, Zai-Sheng
• Wu, Juhong
• Jiang, Lizhi
• Chen, Juanjuan
• Li, Jinyu

Titel

A hydrogen sulfide-responsive prodrug for monitoring real-time release and improving therapeutic effects of anticancer drug SN-38

Ist Teil von

• Sensors and actuators. B, Chemical, 2022-12, Vol.373, p.132750, Article 132750

Ort / Verlag

Lausanne: Elsevier B.V

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• As a topoisomerase I inhibitor, the prodrug irinotecan has been widely used in the chemotherapy of metastatic cancers. However, the transformation from irinotecan to its active metabolite SN-38 is slow and non-selective in cancer cells, which is not desired for clinical oncotherapy. Additionally, the fluorescence turn-on response of irinotecan is poor, prohibiting real-time observations on SN-38 release. Here, we developed a new prodrug (BDD-SN38) that is well suited for real-time monitoring SN-38 release and reducing its activation in normal cells. The fluorescence and activity of BDD-SN38 was significantly quenched by dinitrobenzene group. The in vitro and in cell results showed that BDD-SN38 could be selectively and rapidly activated by hydrogen sulfide (H2S) to obtain significantly enhanced fluorescence and activity. Moreover, BDD-SN38 achieved remarkable toxicity towards H2S-overexpressed cancer cells. Overall, the H2S-responsive prodrug developed here was proved to be a promising candidate for real-time monitoring SN-38 release and improving its therapeutic effect. [Display omitted] •A hydrogen sulfide responsive prodrug was designed and synthesized.•BDD-SN38 can be rapidly activated by H2S.•BDD-SN38 can obtain significantly enhanced fluorescence in H2S over-expressed cancer cells.•BDD-SN38 can achieve enhanced toxicity towards H2S over-expressed cancer cells.•BDD-SN38 can reduce toxicity towards normal cells.