Dual-Targeting Dual-Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Yang Zhi
  • Bertrand Czarny
  • Tan Boon Toh
  • Lissa Hooi
  • Edward Kai-Hua Chow
  • Wee Han Ang
  • Dan Gibson
  • Giorgia Pastorin

Detail(s)

Original languageEnglish
Pages (from-to)8109-8114
Journal / PublicationAngewandte Chemie - International Edition
Volume58
Issue number24
Online published3 Apr 2019
Publication statusPublished - 11 Jun 2019
Externally publishedYes

Abstract

A novel and highly efficient dual-targeting platform was designed to ensure targeted in vivo delivery of dual-action PtIV prodrugs. The dual targeting was established by liposomal encapsulation of PtIV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug-loaded liposomes in the tumor. After the release of the PtIV prodrug inside cancer cells, a second stage of targeting directed a portion of the PtIV prodrugs to the mitochondria. Upon intracellular reduction, these PtIV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our PtIV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual-targeting dual-action platform.

Research Area(s)

  • antitumor agents, drug discovery, platinum, prodrugs, sensitizers

Citation Format(s)

Dual-Targeting Dual-Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity. / Babak, Maria V.; Zhi, Yang; Czarny, Bertrand et al.

In: Angewandte Chemie - International Edition, Vol. 58, No. 24, 11.06.2019, p. 8109-8114.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review