Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 28, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202205429
Keywords
Bioinorganic Chemistry; Iridium; Medicinal Inorganic Chemistry; Metals in Medicine; Photodynamic Therapy
Categories
Funding
- National Natural Science Foundation of China [22120102002]
- Science and Technology Innovation Program of Hunan Province of China [2021RC5028]
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This study presents the formulation of a promising Ir-III complex into a biodegradable coordination polymer, which can selectively accumulate in the mitochondria and trigger cell death through hybrid apoptosis and ferroptosis pathways upon irradiation.
The clinical application of photodynamic therapy is hindered by the high glutathione concentration, poor cancer-targeting properties, poor drug loading into delivery systems, and an inefficient activation of the cell death machinery in cancer cells. To overcome these limitations, herein, the formulation of a promising Ir-III complex into a biodegradable coordination polymer (IrS NPs) is presented. The nanoparticles were found to remain stable under physiological conditions but deplete glutathione and disintegrate into the monomeric metal complexes in the tumor microenvironment, causing an enhanced therapeutic effect. The nanoparticles were found to selectively accumulate in the mitochondria where these trigger cell death by hybrid apoptosis and ferroptosis pathways through the photoinduced production of singlet oxygen and superoxide anion radicals. This study presents the first example of a coordination polymer that can efficiently cause cancer cell death by apoptosis and ferroptosis upon irradiation, providing an innovative approach for cancer therapy.
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