A self-immolated fluorogenic agent triggered by H2S exhibiting potential anti-glioblastoma activity. Issue 11 (28th April 2021)

• Record Type: Journal Article
• Authors: Ge, Chao; Li, Ji; Liu, Lu; Liu, Hong-Ke; Qian, Yong
• Is Part Of: Analyst. Volume 146:Issue 11(2021)
• Page Start: 3510
• Page End: 3515
• Publication Date: 2021-04-28
• Subjects: Chemistry, Analytic -- Periodicals; 543
• DOI: 10.1039/d1an00457c
• Languages: English
• ISSNs: 0003-2654

Abstract

Abstract : We have developed a novel H2 S-triggered fluorogenic agent SNF that released the active amonafide with fluorescence via a self-immolative process, which escaped from the lysosome to the nucleus and mainly caused autophagic cell death of glioma cells. Abstract : Glioblastoma is the most common and aggressive type of malignant brain tumor with poor survival and limited therapeutic options. Theranostic anticancer agents with dual functions of diagnosis and therapy are highly attractive. Self-immolation reaction is a promising approach for theranostic prodrugs triggered by the tumor microenvironment. Overexpression of hydrogen sulfide (H2 S) in glioma cells becomes a potential stimulus for activating prodrugs. Herein, a novel H2 S responsive agent (SNF) containing amonafide (ANF), a self-immolative linker and a trigger group has been developed for imaging and chemotherapy in living cells. SNF exhibited high selectivity and sensitivity towards H2 S and also showed excellent lysosome-targeted capability. The activated SNF could translocate to the nucleus, causing DNA damage and blocking the cell cycle. More mechanistic studies indicated that SNF altered the mitochondrial membrane potential and induced autophagy in human glioblastoma-astrocytoma (U87MG). In addition, 3D multicellular U87MG tumor spheroids were used to further confirm the active drug release and high anti-proliferative activity of SNF. This approach may provide a general strategy for developing H2 S-triggered prodrugs for synergic cancer therapy.