Smart One‐for‐All Agent with Adaptive Functions for Improving Photoacoustic /Fluorescence Imaging‐Guided Photodynamic Immunotherapy

Abstract Multifunctional phototheranostics that integrate several diagnostic and therapeutic strategies into one platform hold great promise for precision medicine. However, it is really difficult for one molecule to possess multimodality optical imaging and therapy properties that all functions are in the optimized mode because the absorbed photoenergy is fixed. Herein, a smart one‐for‐all nanoagent that the photophysical energy transformation processes can be facilely tuned by external light stimuli is developed for precise multifunctional image‐guided therapy. A dithienylethene‐based molecule is designed and synthesized because it has two light‐switchable forms. In the ring‐closed form, most of the absorbed energy dissipates via nonradiative thermal deactivation for photoacoustic (PA) imaging. In the ring‐open form, the molecule possesses obvious aggregation‐induced emission features with excellent fluorescence and photodynamic therapy properties. In vivo experiments demonstrate that preoperative PA and fluorescence imaging help to delineate tumors in a high‐contrast manner, and intraoperative fluorescence imaging is able to sensitively detect tiny residual tumors. Furthermore, the nanoagent can induce immunogenic cell death to elicit antitumor immunity and significantly suppress solid tumors. This work develops a smart one‐for‐all agent that the photophysical energy transformation and related phototheranostic properties can be optimized by light‐driven structure switch, which is promising for multifunctional biomedical applications.