Related Experiment Video
Updated: Jan 4, 2026
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Identification of two mitochondrial-targeting cyclometalated iridium(III) complexes as potent anti-glioma stem cells
Wan Peng1, Ahmed M Hegazy2, Ning Jiang1
1Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Abstract:
Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 μM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.
Insights
Two iridium(III) complexes show potential as glioblastoma stem cell (GSC) therapeutics. These compounds selectively kill GSCs by inducing mitochondrial-mediated apoptosis and inhibiting self-renewal, offering a promising avenue for GBM treatment.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Nanotechnology
Background:
- Glioma stem cells (GSCs) drive glioblastoma multiforme (GBM) recurrence and invasion.
- Targeting GSCs is crucial for effective GBM therapy.
- Cyclometalated iridium(III) complexes are explored for anticancer potential.
Purpose of the Study:
- To investigate the antitumor activity of two cyclometalated iridium(III) complexes against GSCs.
- To elucidate the mechanism of action of these iridium complexes in GSCs.
Main Methods:
- Synthesis and characterization of two iridium(III) complexes: [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2).
- Evaluation of cytotoxicity against GSCs, determining IC50 values.
- Mechanistic studies including GSC proliferation assays, cellular uptake, mitochondrial localization, apoptosis induction (MMP loss, ROS elevation, caspase activation), and colony formation assays.
Main Results:
- Ir1 and Ir2 exhibited selective cytotoxicity against GSCs with IC50 values between 5.26-9.05 μM.
- The complexes suppressed GSC proliferation, penetrated GSCs efficiently, and localized to mitochondria.
- Ir1 and Ir2 induced mitochondria-mediated apoptosis and impaired GSC self-renewal and proliferation capacity.
Conclusions:
- Cyclometalated iridium(III) complexes Ir1 and Ir2 demonstrate significant antitumor activity against GSCs.
- These complexes induce apoptosis via mitochondrial pathways and inhibit GSC self-renewal.
- This study represents the first investigation into the anti-GSC properties of cyclometalated iridium(III) complexes, highlighting their therapeutic potential for GBM.
More Related Videos
10:28Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
Published on: January 10, 2018
11:13MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells
Published on: February 22, 2017
