A Fluorescent Probe for Investigating the Activation of Anticancer Platinum(IV) Prodrugs Based on the Cisplatin Scaffold

Abstract

Watching closely: A fluorescent probe was engineered to detect the clinically relevant platinum drug cisplatin within a complex cellular environment, thus providing a direct means for visualizing its cell entry and the activation of platinum(IV) prodrugs in cancer cells.

Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid

“…While no direct correlation between the reduction potential and prodrug efficacy has been established in the literature, a reduction potential in the mid-range as observed for complexes with two axial carboxylate ligands (~− 600 mV) seems to be a good guideline for an effective Pt(IV) prodrug [1]. The reduction of Pt(IV) complexes has been investigated in the past with different techniques and under different conditions [47][48][49][50][51]. It is generally presumed that under physiological conditions Pt(IV) is reduced by low-molecular-weight reducing agents such as ascorbic acid or glutathione, although recently evidence has been obtained that higher molecular weight biomolecules such as metallothioneines can also play a major role in the reduction and activation of Pt(IV) prodrugs [52].…”

Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast

“…12 The intracellular reduction has been demonstrated by XANES spectroscopy and fluorescence techniques. [13][14][15] It has been reported that the physicochemical properties of Pt(IV) complexes, such as aqueous solubility or lipophilicity, can be tuned by modification of the axial substituents. 16 Tranilast is commercialized as an antiallergy drug used for the treatment of inflammatory diseases.…”

Photoinduced Reduction of PtIVwithin an Anti-Proliferative PtIV-Texaphyrin Conjugate

“…It is thus consistent with the model studies using 3 and 5′-GMP noted above and is in line with recently published studies of Pt(IV) complexes. [15] Nevertheless, even under conditions of photoirradiation with laboratory light, conjugate 4 is much less reactive towards DNA than cisplatin. This finding is thought to reflect the slow light-induced reduction kinetics operative in the case of species such as 3 and 4 and the corresponding release of only a few active platinum(II) complexes at a time.…”