Manipulating ICG <i>J</i>‐Aggregation and Disaggregation for Imaging‐Guided Cancer Therapy with Self‐Reporting Efficiency

Integrating imaging guided therapy and therapeutic effect self-reporting would highly benefit clinic applications. J-type aggregates of organic dyes with corresponding photothermal effect have made them popular agents for photoacoustic (PA) imaging and photothermal therapy (PTT). However, approaches to manipulate the disaggregation of J-aggregate with corresponding organic dye fluorescence recovery have rarely been reported, which limits the full exploration of J-aggregate in therapeutic applications. Herein, indocyanine green (ICG) J-aggregate is designed in a micelle structure (J-ICG-Micelle) by co-assembling ICG with DSPE-Pep-PEG, which contains peptide KADEVDAC that recognized and cleaved by caspase-3. Taking advantages of the red-shifted absorbance of J-ICG-Micelle, it achieves PA imaging navigated delivery process with an indication of tumor accumulation time and position to perform PTT. Corresponding cell apoptosis and caspase-3 generation cleaves peptide KADEVDAC and results in fluorescence recovery of ICG, which self-reports therapeutic effect in real time, and the intensity for fluorescence recovery demonstrates similar tendency as H&E staining at tumor sections. The as-presented J-ICG-Micelle would have a promising contribution to precise cancer therapy.