The Platin-X series: activation, targeting, and delivery

Abstract

Anticancer platinum (Pt) complexes have long been pronounced as one of the biggest success stories in the history of medicinal inorganic chemistry. Yet there still remains the hunt for the “magic bullet” which can satiate the requisites of an effective chemotherapeutic drug formulation. Pt(IV) complexes are kinetically more inert that the Pt(II) congeners and offer the opportunity to append additional functional groups/ligands for prodrug activation, tumor targeting or drug delivery. The ultimate aim for functionalization is to enhance the tumor selective action and attenuate systemic toxicity of the drugs. Moreover, increase in cellular accumulation to surmount the resistance of the tumor against the drugs is also of paramount importance in drug development and discovery. In this review, we will address some of the attempts in our lab to develop Pt(IV) prodrugs that can be activated and their targeted delivery using robust nanotechnology platforms.

Protected and De-protected Platinum(IV) Glycoconjugates With GLUT1 and OCT2-Mediated Selective Cancer Targeting: Demonstrated Enhanced Transporter-Mediated Cytotoxic Properties in vitro and in vivo

“…Platinum(IV)-based anticancer prodrugs can overcome the limitations of platinum(II) drugs such as cisplatin, carboplatin, and oxaliplatin, which are widely used clinically (Wang and Lippard, 2005 ; Kelland, 2007 ; Wheate et al, 2010 ) Recently, platinum(IV) prodrugs as candidates have been designed, synthesized and evaluated as antitumor agents (Wang et al, 2015 ; Johnstone et al, 2016 ). Most platinum(IV) drugs with dual axial ligands offer the opportunity to append additional functional groups for pro-drug activation, tumor targeting, or drug delivery (Basu et al, 2016 ). Compared with platinum(II) complexes, platinum(IV) complexes not only exhibit increased stability and reduced side effects but also facilitate the intravenous-to-oral switch in cancer chemotherapy (Han et al, 2015 ).…”

Probing the Interactions of Cytotoxic [Pt(1S,2S‐DACH)(5,6‐dimethyl‐1,10‐phenanthroline)] and Its PtIV Derivatives with Human Serum

“…Pt IV complexes are inert octahedral complexes prepared by oxidative addition of the square‐planar Pt II drugs. The axial ligands are used to improve the pharmacological properties of the prodrug . Pt IV prodrugs are believed to be stable in the blood and to be activated inside the cancer cells by reduction, releasing the original platinum drugs and the two axial ligands.…”

“…The axial ligandsa re used to improve the pharmacological properties of the prodrug. [18] Pt IV prodrugs are believed to be stable in the blood and to be activated inside the cancer cells by reduction,releasingt he originalplatinum drugs and the two axial ligands. More recently,t he preparation,c haracterization, diffusion characteristics and cytotoxic properties of the Pt IV derivatives of Pt56MeSS and Pt56MeRRw ith two axial hydroxidol igands was described.…”

Dose-finding study of oxaliplatin associated to capecitabine-based preoperative chemoradiotherapy in locally advanced rectal cancer

“…These new compounds would be able to target specific cellular structures, carrying the pharmacological action only at the site of interest and reducing the involvement of healthy structures. Among the main examples of this strategy we find platinum A able to specifically bind the oxygenase-2 cycle (COX-2) while platinum B is able to interact with mitochondrial DNA by interfering with tumor resistance mechanisms [ 1 ].…”