PlatinER : A Highly Potent Anticancer Platinum(II) Complex that Induces Endoplasmic Reticulum Stress Driven Immunogenic Cell Death

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

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Detail(s)

Original languageEnglish
Pages (from-to)19070-19078
Journal / PublicationAngewandte Chemie - International Edition
Volume59
Issue number43
Online published27 Jul 2020
Publication statusPublished - 19 Oct 2020

Abstract

Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can improve the clinical outcomes of chemo-immunotherapeutic combination regimens through the establishment of a long-term cancer immunity. None of the clinically used DNA-binding PtII complexes is considered a Type II ICD inducer. We generated a series of PtII-carbene complexes by applying minor structural alterations to the scaffold of a Type II ICD inducer Pt-NHC and compared their efficiency in triggering ICD-related cellular responses and phagocytosis. We successfully identified PlatinER, a novel highly potent PtII candidate with superior ICD properties. Crucially, the magnitude of ICD-associated phagocytosis induced upon exposure of cancer cells to Pt complexes was dependent on the levels of ER-localized reactive oxygen species (ROS) generation, which underpins their mechanisms of action and provides a feasible approach for the design of more effective Type II ICD inducers.

Research Area(s)

  • antitumor agents, drug discovery, immunochemotherapy, immunogenic cell death, platinum

Citation Format(s)

PlatinER : A Highly Potent Anticancer Platinum(II) Complex that Induces Endoplasmic Reticulum Stress Driven Immunogenic Cell Death. / Tham, Max Jing Rui; Babak, Maria V.; Ang, Wee Han.

In: Angewandte Chemie - International Edition, Vol. 59, No. 43, 19.10.2020, p. 19070-19078.

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