Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy

Abstract

Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy.

Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic Eradication of Patient‐Derived Lung Cancer

“…SD‐NP without DMC was less potent than DD‐NP, indicating the synergy of DMC with Pt in vivo. Specifically, the tumor size was about 750 mm 3 in DD‐NP group while 2100 mm 3 in SD‐NP group after 18 d. Cisplatin is known to severely damage kidneys hence it is toxic to animals . Here all the tested mice groups demonstrated 13.3% to 16.2% body weight increase except cisplatin treated one with 14.8% body weight loss at day 8, indicating the lower systemic toxicity of DD‐NP than cisplatin (Figure B).…”

An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo

“…From a chemical point of view, the two additional ligands of octahedral platinum( iv ) compounds offer a broad range of possibilities to modify such compounds and to fine-tune their pharmacological properties like lipophilicity or solubility. 8 Nevertheless, only a few of a countless number of platinum( iv ) compounds prepared ended in clinical trials, with satraplatin as the most prominent representative. Satraplatin reached a clinical phase III study in combination with prednisone, called SPARC (satraplatin and prednisone against hormone-refractory prostate cancer) trial.…”

Platinum(II) Complexes of Curcumin Showing Photocytotoxicity in Visible Light

“…Such attempts were made by changing the leaving groups and modulating the ligand‐dissociation kinetics. In addition, inert platinum(IV) prodrugs are designed to generate active species by reduction in intracellular environment in the presence of glutathione or ascorbic acid . By tuning the axial ligands of these platinum(IV) complexes, targeted and improved antiproliferative properties in cancer cells were achieved .…”