Issue 38, 2022

A platinum–ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors

Abstract

Regulation of tumor hypoxia and redox homeostasis is a promising strategy for cancer therapy. Nanocatalytic medicine has played more and more important roles in this field because it can cleverly convert the efficiency and selectivity of catalysis into high therapeutic efficiency. Herein, we developed a platinum(IV)–ruthenium hybrid prodrug, named as Pt–Ru, for efficient chemo-catalytic synergistic therapy of hypoxic tumors. The ruthenium hybridization endowed the Pt(IV) prodrug with multi-enzyme catalytic activity, that is, mimicking catalase (CAT) to generate O2in situ, mimicking peroxidase (POD) to produce reactive oxygen species, and mimicking glutathione peroxidase (GPx) to deplete GSH, thus effectively overcoming tumor hypoxia and cisplatin resistance. As a result, Pt–Ru treatment led to a superior anticancer efficacy to cisplatin both in vitro and in vivo. This work suggested redox homeostasis regulation as a tantalizing angle for developing the next generation of platinum drugs.

Graphical abstract: A platinum–ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors

Supplementary files

Article information

Article type
Edge Article
Submitted
16 Jun 2022
Accepted
14 Aug 2022
First published
09 Sep 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 11360-11367

A platinum–ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors

G. Yang, X. Su, B. Liang, Z. Pan, Q. Cao and Z. Mao, Chem. Sci., 2022, 13, 11360 DOI: 10.1039/D2SC03375E

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