A Lipophilic Pt(IV) Oxaliplatin Derivative Enhances Antitumor Activity

Abstract

Side effects and acquired resistance by cancer cells limit the use of platinum anticancer drugs. Modification of oxaliplatin (OXA) into a lipophilic Pt(IV) complex [Pt(DACH)(OAc)(OPal)(ox)] (1), containing both lipophilic and hydrophilic axial ligands, was applied to improve performance and facilitate incorporation into polymeric nanoparticles. Complex 1 exhibited unique potency against a panel of cancer cells, including cisplatin-resistant tumor cells. [Pt(DACH)(OAc)(OPal)(ox)] incorporated nanoparticles (2) presented a mean diameter of 146 nm with encapsulation yields above 95% as determined by HPLC. Complexes 1 and 2 showed enhanced in vitro cellular Pt accumulation, DNA platination, and antiproliferative effect compared to OXA. Results of an orthotopic intraperitoneal model of metastatic ovarian cancer (SKOV-3) and a xenograft subcutaneous model of colon (HCT-116) tumor in SCID-bg mice showed that the activity of 1 and 2 significantly decreased tumor growth rates compared to control and OXA treatment groups. Consequently, these findings warrant further development toward clinical translation.

Palladium(ii) complexes with thiosemicarbazones derived from pyrene as topoisomerase IB inhibitors

“…New metal complexes might have increased efficacy and the possibility of overcoming resistance, which are the major limitations of the platinum anticancer drugs used in chemotherapy. 15,16 In this regard, palladium complexes are natural analogues of platinum. However, palladium complexes usually exhibit high lability towards ligand exchange which limits their use.…”

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

“…S1 †). 49 PtC 10 is less water soluble than OX, presumably due to the presence of the hydrophobic alkyl chain. Because of this reduced water solubility, the host-guest complexation interactions between CP6A and PtC 10 could not be investigated directly by NMR spectroscopy in D 2 O.…”

Anticancer platinum‐based complexes with non‐classical structures

“…These findings may pave the way for the discovery of new Pt(IV) prodrugs with highly predictable and tuned properties although the exact mechanisms and laws have not been confirmed. Ammar and co‐workers also designed a new Pt(IV) oxaliplatin derivative with both lipophilic and hydrophilic ligands in the axial positions ( 64 ; Figure ). The cytotoxicity of 64 was substantially greater than that of oxaliplatin against both platinum‐sensitive and platinum‐resistant cell lines, as a result of its enhanced accumulation and its lipophilic character.…”