Photo-triggered Zn²⁺ release for the regulation of zinc enzymes

Zinc ions (Zn²⁺) play a critical role in the regulation of zinc enzymes and cell metabolism. However, previous Zn²⁺ delivery methods are usually based on pH-responsive zinc coordination complexes, which are difficult for the precise control of Zn²⁺ release at desired locations. To tackle this challenge, we herein developed a photo-triggered Zn²⁺ release system based on HBTH–Zn–TAT nanoparticles (NPs) with 2-(2-hydroxyphenyl)-benzothiazolines (HBTH) as the Zn²⁺ ligand, DSPE–PEG/DSPE–PEG–Mal polymers as the matrix and TAT peptide as the cell penetrating ligand. HBTH–Zn–TAT NPs can quickly release Zn²⁺ under white light irradiation and efficiently regulate extra- and intracellular zinc enzyme activities, such as carbonic anhydrase, caspase-3 and protein phosphatase type 2A (PP2A). Based on the advantages of the photo-triggered release of Zn²⁺ with a high spatiotemporal resolution, HBTH–Zn–TAT NPs are promising for the regulation of zinc enzymes and corresponding bioactivities.