Evaluation of erastin synergized cisplatin anti-nasopharyngeal carcinoma effect with a glutathione-activated near-infrared fluorescent probe

Nasopharyngeal carcinoma (NPC), a malignant tumor originating from the nasopharynx, is one of the common malignant tumors of the head and neck. There are significant geographical differences in the incidence of nasopharyngeal carcinoma, with a high incidence in China and Southeast Asian countries. Herein, we designed and synthesized a novel near-infrared fluorescent (NIRF) probe to detect glutathione (GSH) in cellular and tumor environments using semi-naphthofluorescein (SNAFL) as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety. Upon reaction with GSH, SNAFL-GSH emitted a fluorescence signal, and its emission wavelength at 650 nm was remark-ably enhanced. The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys, Hcy, and H2S. Moreover, SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference. At the cellular level, cisplatin (DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines (CNE2, CNE1, 5-8F cells) by erastin combined with DDP were visualized with the help of SNAFL-GSH. In a mouse tumor xenograft model, we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC. More importantly, the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80 mu m. It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC, and these results would also provide new ideas for the clinical treatment of NPC.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck, with a high incidence in China and Southeast Asian countries. In this study, a novel near-infrared fluorescent probe, SNAFL-GSH, was designed and synthesized for the detection of glutathione (GSH). The probe showed selective detection of GSH and the ability to distinguish normal and cancer cells. It has great potential for application in the diagnosis and evaluation of NPC.