Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Abstract

Platinum-based anticancer drugs are a class of widely used agents in clinical cancer treatment. However, their efficacy was greatly limited by their severe side effects and the arising drug resistance. The selective activation of inert platinum-based drugs in the tumor site by light irradiation is able to reduce side effects, and the novel mechanism of action of photoactivatable platinum drugs might also conquer the resistance. In this review, the recent advances in the design of photoactivatable platinum-based drugs were summarized. The complexes are classified according to their mode of action, including photoreduction, photo-uncaging, and photodissociation. The rationale of drug design, dark stability, photoactivation process, cytotoxicity, and mechanism of action of typical photoactivatable platinum drugs were reviewed. Finally, the challenges and opportunities for designing more potent photoactivatable platinum drugs were discussed.

Are smart delivery systems the solution to overcome the lack of selectivity of current metallodrugs in cancer therapy?

“…29,31,[44][45][46] In contrast, only a few stimulus-dependent systems have been described for the targeted delivery of platinum drugs into cancer cells so far. In particular, there are some examples of systems that are triggered by an external stimulus (such as near-infrared, ultraviolet or visible photoresponsive systems) 22,30,[47][48][49][50] but the great part of them are sensitive to tumour-related stimuli, namely to the differences in the pH levels and the redox potential existing between healthy and cancer tissues.…”

Ligand Evolution in the Photoactivatable Platinum(IV) Anticancer Prodrugs

“…In recent years, a number of excellent reviews on the advances of photoactivated anticancer Pt(IV) prodrugs have been published. They focused on various aspects of this unique family of prodrugs, for instance, synthesis ( Wilson and Lippard, 2014 ; Xu et al, 2021b ), phototherapy potency ( Gurruchaga-Pereda et al, 2019 ; Imberti et al, 2020 ), photoactivation mode and mechanism of action ( Dai and Wang, 2020 ; Xu et al, 2021b ), axial substitutions and modifications, and delivery ( Johnstone et al, 2016 ; Kenny and Marmion, 2019 ; Ravera et al, 2019 ; Jia et al, 2021 ) either in general view of Pt-based anticancer complexes ( Imran et al, 2018 ; Ravera et al, 2022 ) or in a specific view of a subgroup, for example, diazido-type Pt(IV) prodrugs ( Shi et al, 2019 ; Mu et al, 2021 ). However, few articles have presented a comprehensive summary and review on the evaluation of the coordinated ligands, namely, non-leaving ligands, leaving ligands, and axial ligands ( Wilson and Lippard, 2014 ), in photoactivated anticancer Pt(IV) prodrugs.…”

Oxaliplatin-Induced Neuropathy: Genetic and Epigenetic Profile to Better Understand How to Ameliorate This Side Effect

“…Within this framework, new platinum analogs have been developed. Although other new platinum-derived drugs are under study (Johnstone et al, 2016;Dai and Wang, 2020), nowadays, carboplatin and oxaliplatin are the most widely used in clinical practice (Fischer and Ganellin, 2006).…”