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

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Chinese Chemical Letters 2024年第2期35卷 311-316页

作者： Rong He Dandan Tang Ningge Xu Heng Liu Kun Dou Xuejun Zhou Fabiao Yu Department of Otolaryngology Head and Neck SurgeryThe First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China Key Laboratory of Hainan Trauma and Disaster Rescue Key Laboratory of Emergency and TraumaMinistry of EducationEngineering Research Center for Hainan Bio-Smart Materials and Bio-Medical DevicesCollege of Emergency and TraumaHainan Medical UniversityHaikou 571199China Sichuan Provincial General Hospital of Judicial Police Chengdu 610225China

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 remarkably enhanced.The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys,Hcy,and H_(2) S.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 80µm.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.

关键词： Glutathione NIRF probe Ferroptosis anti-tumor therapy evaluation Bioimaging

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