In Situ Sonoafterglow Supramolecular Hydrogel From Natural Substrate for Post‐Surgical Glioblastoma Treatment

ABSTRACT Fluorescence imaging suffers from substantial background interference and a low signal‑to‑background ratio due to real‑time excitation. In contrast, afterglow luminophores enable prolonged emission after excitation ceases, effectively suppressing biological background noise and enhancing the imaging signal‑to‑background ratio. However, existing afterglow probes are largely limited to nanoparticles of semiconducting polymer or synthetic organic molecules, with no report of a natural‐product‐derived afterglow system in hydrogel form. This study pioneers the discovery that chlorogenic acid (CA), a natural antitumor agent, exhibits unique sonoafterglow properties. This finding prompted the design of a CA prodrug capable of self‑assembling in water into a CA‑based supramolecular hydrogel—representing the first example of a sonoafterglow hydrogel rather than conventional nanoparticle formulations. The VP@Pro‑CA gel formulation, which incorporates the sonosensitizer verteporfin (VP), allows post‑operative local injection for sonodynamic therapy (SDT) to prevent glioblastoma (GBM) recurrence. Crucially, the ONOO − ‑triggered afterglow emission enables real‑time therapeutic monitoring, demonstrating exceptional potential for GBM theranostics. Notably, CA constitutes a novel class of biosafe, small‑molecule sonoafterglow substrates with intrinsic pharmacological activity, offering unparalleled advantages for clinical translation in this emerging field.