A Concerted Enzymatic and Bioorthogonal Approach for Extra- and Intracellular Activation of Environment-Sensitive Ruthenium(II)-Based Imaging Probes and Photosensitizers

16 May 2023

Published on Angewandte Chemie (16 May 2023)

Author(s): Justin Shum, Dr. Lawrence Cho-Cheung Lee, Michael Wai-Lun Chiang, Dr. Yun-Wah Lam, Prof. Kenneth Kam-Wing Lo

Abstract

In this article, we report a novel targeting strategy involving the combination of an enzyme-instructed self-assembly (EISA) moiety and a strained cycloalkyne to generate large accumulation of bioorthogonal sites in cancer cells. These bioorthogonal sites can serve as activation triggers in different regions for transition metal-based probes, which are new ruthenium(II) complexes carrying a tetrazine unit for controllable phosphorescence and singlet oxygen generation. Importantly, the environment-sensitive emission of the complexes can be further enhanced in the hydrophobic regions offered by the large supramolecular assemblies, which is highly advantageous to biological imaging. Additionally, the (photo)cytotoxicity of the large supramolecular assemblies containing the complexes was investigated, and the results illustrate that cellular localization (extracellular and intracellular) imposes a profound impact on the efficiencies of photosensitizers.

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Figure 1
Schematic illustration of EISA of small self-assembling motifs to generate large supramolecular assemblies with many bioorthogonal sites and upon bioorthogonal reaction leads to greatly enhanced emission intensity, lifetime extension, and singlet oxygen generation.