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

Abstract 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.