Platinum(IV) antitumor complexes and their nano-drug delivery

19F NMR Allows the Investigation of the Fate of Platinum(IV) Prodrugs in Physiological Conditions

“…[13] Briefly,a fter oxidation of cisplatin to the di-hydroxido intermediate cis,cis,trans-[PtCl 2 (NH 3 ) 2 (OH) 2 ]( oxoplatin, Scheme 1) by H 2 O 2 ,o ne hydroxido ligand of oxoplatin was substituted by FBAu sing the 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxy-succinimide (EDC/NHS) method. Pt-FBA was purified by ether/acetone precipitation and fully characterized by high-performance liquid chromatography (HPLC), electrospray mass spectrometry (ESI-MS), and 1 Ha nd 19 FNMR spectroscopy (Figures S1 and S2).…”

“…Cisplatin (cis-[PtCl 2 (NH 3 ) 2 ], Scheme 1) is aw idely used anticancer drug for the treatment of awide variety of human malignancies.P rospective alternatives to cisplatin in cancer treatment are the more inert, six-coordinated Pt IV prodrugs (cis,cis,trans-[PtCl 2 (NH 3 ) 2 (X)(Y)] complexes) which could overcome the drawbacks of conventional Pt II drugs stemming from non-specific reactions with other physiological substrates. [1] Afirst example was satraplatin (Scheme 1), an orally available Pt IV drug that has entered phase III clinical trial. [2] Moreover,t he two additional axial ligands of Pt IV prodrugs provide the possibility to introduce tumor targeting and/or additional pharmacologically active entities that could further enhance drug efficacy.Therefore,alarge variety of Pt IV agents have been synthesized and proven to be endowed with prominent antitumor efficacy.…”

Pt(iv) antitumor prodrugs: dogmas, paradigms, and realities

“…To provide a comprehensive view of this specific topic is beyond the purposes of the present paper since several excellent, exhaustive recent reviews have dealt with multi-action Pt (IV) prodrugs. [20][21][22][23][24][25][26] Let us cite just two first-borns of the Pt(IV) bifunctional family, which have prompted important series of homologues: Dyson's ethacraplatin (containing the glutathione transferase, GST, inhibitor ethacrynic acid) 27 and Lippard's mitaplatin (containing the pyruvate dehydrogenase kinase, PDK, inhibitor dichloroacetic acid). 28 Additionally, the complexes known as either platin-A 29 or asplatin, 30 reported independently by two research groups (containing acetylsalicylic acid, an inhibitor of cyclooxygenase, COX), have been the precursors of a multitude of Pt(IV) assemblies containing non-steroidal anti-inflammatory drugs (NSAIDs).…”

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.…”