Journal Article

Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy

Chao, Hui, Stang, Peter J., Liu, Jiangping, Zhou, Zhixuan, Li, Xiaopeng, Rees, Thomas W., Wang, Heng

2018

Overview

As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru–Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.

• Publisher: National Academy of Sciences
• Subject: A549 Cells / Absorption / Absorption cross sections / Animals / Apoptosis / Atoms & subatomic particles / Cell death / Cell Survival - drug effects / Chemistry / Coordination Complexes - chemistry / Coordination Complexes - pharmacology / Cytotoxicity / Deoxyribonucleic acid / DNA / HeLa Cells / Humans / In vivo methods and tests / Internalization / Mice / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Mitochondrial DNA / Near infrared radiation / Nuclei (cytology) / Organometallic compounds / Oxygen / Photochemotherapy - methods / Photodynamic therapy / Photoexcitation / Photon absorption / Photons / Photosensitizing Agents - chemistry / Photosensitizing Agents - pharmacology / Physical Sciences / Platinum - chemistry / Platinum - pharmacology / Reactive oxygen species / Ruthenium / Ruthenium - chemistry / Ruthenium - pharmacology / Self-assembly / Side effects / Singlet oxygen / Singlet Oxygen - metabolism / Singlet Oxygen - pharmacology / Tumors / Xenograft Model Antitumor Assays