Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance

Abstract

Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well-defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future.

Recent Advances in the Chemistry of Metal Carbamates

“…More precisely, coupling of a Pt(IV) (bis)hydroxo species with an alkyl or aryl isocyanate affords the corresponding (bis)carbamate. Following optimization [ 260 ], allowing the reaction to be conducted in dimethylformamide and not in neat isocyanate, more than 60 different Pt(IV) species were thus prepared, arousing interest as possible anticancer agents (see Section 5 ) [ 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 ].…”

Pt(II) complexes immobilized on polymer‐modified magnetic carbon nanotubes as a new platinum drug delivery system

“…Because of these limitations, extensive research in order to develop new platinum compounds with a wide range of capabilities, including antitumour activity, reduced side effects and improved pharmacokinetic properties, has been carried out . Although platinum‐based anticancer drugs are highly effective in treating and controlling, there are some disadvantages, such as low solubility in aqueous environments, causing clinical applications of these compounds to be problematic . Thus, it is of great significance to introduce delivery systems to improve the low hydrophilicity of platinum‐based anticancer drugs.…”

pH/redox sensitive nanoparticles with platinum(iv) prodrugs and doxorubicin enhance chemotherapy in ovarian cancer

“…6, the free Pt and free Dox led to increased cell cycle arrest in the S phase and G 2 /M phase respectively, which was consistent to previous studies. 23,24 The S phase arrest of NPs (Pt(IV)) was superior to free Pt treatment. On the other hand, the G 2 /M phase arrest of free Dox was stronger than NPs (CAD).…”