Cell-specific activation of gemcitabine by endogenous H₂S stimulation and tracking through simultaneous fluorescence turn-on

Abstract

Endogenous H2S-driven theranostic H2S-Gem have been invented. The theranostic prodrug H2S-Gem is selectively activated in cancer cells, releasing active gemcitabine with a simultaneous fluorescence turn-on. H2S-Gem selectively inhibited cancer cell...

Glutathione‐triggered prodrugs: Design strategies, potential applications, and perspectives

“…Accordingly, a bioreversible linkage (e.g., the GSH trigger, i.e., discussed in this review) attached to the self‐immolating spacer can be utilized to facilitate the connection of a broad range of tertiary and heteroaryl amine‐containing drugs for prodrug‐based therapeutic interventions. Moreover, for the vast majority of drugs lacking intrinsic fluorescent properties, the incorporation of self‐immolating spacers that exhibit fluorescence upon activation represents a widely employed strategy 82,235–239 . Nonetheless, a significant challenge arises from the suboptimal performance of these commonly used self‐immolating spacer groups in vivo imaging, owing to their emission wavelengths typically falling below 500 nm.…”

“…Moreover, for the vast majority of drugs lacking intrinsic fluorescent properties, the incorporation of self-immolating spacers that exhibit fluorescence upon activation represents a widely employed strategy. 82,[235][236][237][238][239] Nonetheless, a significant challenge arises from the suboptimal performance of these commonly used self-immolating spacer groups in vivo imaging, owing to their emission wavelengths typically falling below 500 nm. Hence, the quest for self-immolating moieties emitting within the NIR region becomes particularly imperative.…”

Hydrogen sulfide‐activatable fluorescence turn‐on azide‐containing naphthalimide derivative

“…Herein, we report an azide‐containing naphthalimide derivative that can serve as a fluorescence turn‐on Probe 1 for H 2 S in aqueous condition (pH 7.4 PBS solution 10 mM including 40% of dimethyl sulfoxide [DMSO], 37°C). As illustrated in Scheme 1, the azide group of Probe 1 can be reduced to a primary amine by H 2 S to produce 4‐aminonaphthalimide derivative 2 and simultaneously exhibit a fluorescent turn‐on driven by intramolecular charge transfer (ICT) 12–15 . Additionally, in the presence of H 2 S, Probe 1 may display a chromogenic change from colorless to yellow.…”

“…As illustrated in Scheme 1, the azide group of Probe 1 can be reduced to a primary amine by H 2 S to produce 4-aminonaphthalimide derivative 2 and simultaneously exhibit a fluorescent turn-on driven by intramolecular charge transfer (ICT). [12][13][14][15] Additionally, in the presence of H 2 S, Probe 1 may display a chromogenic change from colorless to yellow.…”

A mannose-functionalized pillar[5]arene-based supramolecular fluorescent probe for real-time monitoring of gemcitabine delivery to cancer cells

“…Maiti et al reported a GEM-coumarin conjugate that could be selectively activated by the endogenous H 2 S of cancer cells to release drug and fluorescence-enhancing coumarin. 8 Nevertheless, these current approaches are still associated with limitations, such as some prodrug molecules lack targeting, small molecule prodrugs have high blood clearance and vascular permeability compared to nanodrugs, and the addition of fluorophores to nonfluorescent drugs may alter their intracellular distribution. Therefore, designing a new nanodrug delivery system for efficient targeted delivery and the real-time monitoring of GEM is essential to improving its chemotherapeutic efficacy.…”