A Ratiometric Fluorescent Probe for Cisplatin: Investigating the Intracellular Reduction of Platinum(IV) Prodrug Complexes

Abstract

The PtIV prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional PtII drug therapy. However, there is a lack of tools to study how this new class of PtIV drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate PtIV anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its PtIV derivatives, allowing us to probe the intracellular reduction of PtIV prodrug complexes. The correlation between the amount of active PtII species available after intracellular reduction of PtIV complexes and their cytotoxicity and the role glutathione plays in the reduction of PtIV complexes were investigated.

Gd(iii)–Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy

“…[15][16][17][18][19] A variety of groups can be incorporated as axial ligands to allow for tumor targeting, combination therapy, bioimaging, and controlled reduction of the Pt(IV). [20][21][22][23][24][25][26][27][28][29][30][31] Sessler and coworkers were the rst to demonstrate how Gd(III) complexes can be used synergistically with Pt(IV) prodrugs. Their Gd(III)-texaphyrin complexes have been used to increase tumor localization and mediate the reduction of Pt(IV) to Pt(II).…”

“…Several examples of theranostic Pt(IV) prodrug complexes for dual chemotherapy and uorescence imaging have been reported. [24][25][26][27] Some of these probes can provide important information regarding drug delivery and subsequent reduction of the Pt(IV) complex in vitro. However, in vivo uorescence imaging has limited clinical utility.…”

A singlet oxygen self-reporting photosensitizer for cancer phototherapy

“…Some strategies, such as fluorescence resonance energy transfer (FRET), intramolecular charge transfer (ICT) and electronic energy transfer (EET), which can be good choices to realize fluorescence reporting in PDT. [25][26][27] Using these 1 O2 activable structures as linker, the fluorescence can be gradually released as feedback to control the phototherapy process during irradiated period. Unfortunately, the self-reporting PSs have still few research in the past, instead, these 1 O2 sensitive linkers are more commonly used for prodrug release.…”

Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs

“…Previously reported strategies include axial platinum( iv ) coordination of quenched fluorophores such as fluorescein 17 and selective fluorescence reporting from organic probes following reaction with specific platinum( ii ) reduction fragments. 18 Lanthanides provide a significant advantage over purely organic fluorophores, by producing a highly distinctive emission profile when excited, from which background autofluorescence can also be effectively removed through time-gating. 19 …”