Hydrogen sulfide triggered molecular agent for imaging and cancer therapy

Abstract

We developed an activatable molecular agent, PNF, triggered by intracellular H2S in the lysosome to release the therapeutic drug amonafide, which can escape from the lysosome into the nucleus to induce autophagy of cancer cells.

Dual‐Stimuli‐Activatable Hybrid Prodrug for the Self‐Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn‐On Fluorescence

“…In 2021, Qian and co-workers developed hydrogen sulfide (H 2 S)-responsive fluorogenic prodrug PNF of amonafide having lysosomal selectivity (Scheme 1A). [9] The prodrug exhibited potent anticancer activity in cisplatin-resistant cancer cells (A549R and A2780R) and overexpressed p53 and downregulated P-gp upon its activation by the endogenous H 2 S. In 2021, same group reported another H 2 S-triggered prodrug of amonafide exhibiting anti-glioblastoma activity. [10] Subsequently, in 2022, Scanlan and co-workers reported β-galactosidase-triggered glycosylated prodrug 1 of amonafide (Scheme 1A).…”

“…The prodrug effectively delivered the free amonafide in breast cancer cells with enhanced anti‐proliferative activity. In 2021, Qian and co‐workers developed hydrogen sulfide (H 2 S)‐responsive fluorogenic prodrug PNF of amonafide having lysosomal selectivity (Scheme 1A) [9] . The prodrug exhibited potent anticancer activity in cisplatin‐resistant cancer cells (A549R and A2780R) and overexpressed p53 and downregulated P‐gp upon its activation by the endogenous H 2 S. In 2021, same group reported another H 2 S‐triggered prodrug of amonafide exhibiting anti‐glioblastoma activity [10] .…”

A naphthalimide-based peptide conjugate for concurrent imaging and apoptosis induction in cancer cells by utilizing endogenous hydrogen sulfide

“…9 Consequently, there is an active search for theranostic agents to exploit the H 2 S sensing ability and in this context, several detection methods [10][11][12][13][14][15] have been developed in recent years to sense endogenous H 2 S. [16][17][18][19][20] Some fluorescent probes based on naphthalimide 21,22 , rhodamine 23 , fluorescein 24,25 , and cyanine, 26,27 are good in sensitivity and selectivity among others but there are very few reported schemes that can sense endogenous H 2 S and impede cancer cell proliferation at the same time. 28,29 Scheme 1. Depicts synthesis of hydrogen sulfide responsive fluorescent peptide conjugate.…”

A Rational Designed Bioorthogonal Surface-Enhanced Raman Scattering Nanoprobe for Quantitatively Visualizing Endogenous Hydrogen Sulfide in Single Living Cells

“…Fluorescence imaging is the most widely exploited approach for probing H 2 S in biological systems because of its high sensitivity, good spatiotemporal resolution, and noninvasive sensing ability. − Fluorescent probes that operate through reaction-based sensing, ,− such as chemoselective reduction of azides to amines, − provide high selectivity toward H 2 S over other biothiols and have been used to visualize endogenous H 2 S production of living cells and animals. Despite the tremendous progress, most H 2 S-specific fluorescent probes operate in the visible spectral range, where the biological matrix-derived autofluorescence can cause interference.…”