Issue 11, 2023

Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy

Abstract

Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by their inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop a series of Ru(II) metallacycles (Ru1–Ru4), while simultaneously reducing dark toxicity and enhancing phototoxicity, thus obtaining a high phototoxicity index (PI). These metallacycles enable deep-tissue (∼7 mm) fluorescence imaging and reactive oxygen species (ROS) production and exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 has the lowest dark toxicity, highest ROS generation ability and an optimal PI (∼146). Theoretical calculations verify that Ru4 exhibits the largest steric bulk and the lowest singlet–triplet energy gap (ΔEST, 0.62 eV). In vivo studies confirm that Ru4 allows for effective and safe phototherapy against A549 tumors. This work thus is expected to open a new avenue for the design of high-performance metal-based photosensitizers for potential clinical applications.

Graphical abstract: Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy

Supplementary files

Article information

Article type
Edge Article
Submitted
19 12月 2022
Accepted
06 2月 2023
First published
08 2月 2023
This article is Open Access

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

Chem. Sci., 2023,14, 2901-2909

Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy

C. Li, L. Tu, J. Yang, C. Liu, Y. Xu, J. Li, W. Tuo, B. Olenyuk, Y. Sun, P. J. Stang and Y. Sun, Chem. Sci., 2023, 14, 2901 DOI: 10.1039/D2SC06936A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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