Work

Accelerating Intramolecular Nonradiative Decay via GSH‐Triggered Reassembly of Semiconducting Polymer Nanoprobes for Activatable NIR‐II Phototheranostics

Year: 2026

Type: article

Abstract: ABSTRACT The development of activatable near‐infrared‐II (NIR‐II) photoacoustic and photothermal probes is of great significance for advancing precision phototheranostics toward deep‐seated diseases. Despite our preliminary success in enabling semiconducting polymer nanoprobes (SPNs)‐based activatable NIR‐II photoacoustic imaging (PAI) and photothermal therapy (PTT), this design strategy still requires complicated and time‐consuming chemical syntheses to incorporate activatable groups into the hydrophobic semiconducting backbone, leading to their encapsulation within the nanoprobe core and consequently compromise the responsiveness toward pathological factors in biological environment. Herein, we report a novel activatable SPN (SPN 0 ) that enables glutathione (GSH)‐triggered size transition for amplified NIR‐II PAI and PTT. The SPN 0 was prepared by nanoprecipitation of a diketopyrrolopyrrole‐thiadiazoloquinoxaline semiconducting polymer with a GSH‐responsive amphiphilic matrix. Upon GSH activation, the SPN 0 undergoes a reassembly process to increase the nanoparticle size. Excited‐state dynamics investigations reveal that GSH‐triggered reassembly accelerates intramolecular nonradiative decay in the nanoprobes, which contributes to the enhanced NIR‐II photoacoustic and photothermal performance. In vitro and in vivo studies demonstrate GSH‐activated NIR‐II PAI and PTT toward cancer with high specificity and biosafety. This reassembly strategy provides a convenient and efficient approach to construct activatable NIR‐II phototheranostic nano‐agents, advancing the development of precision medicine.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.2537165