Fine‐Tuning Cu (II)‐Induced Self‐Assembly of Hydrophilic Cyanine Dyes for Enhanced Tumor Photothermal Therapy

Abstract

Abstract Supramolecular self‐assembly of near‐infrared (NIR) dyes are believed to be a promising strategy to design effective photothermal agents for tumor photothermal therapy (PTT). However, due to the uncontrollable intermolecular interactions, accurately fine‐tuning the aggregated morphology of NIR dyes through adjusting their supramolecular self‐assembly is challenging. Here, based on organic–metal coordination interaction, a facile self‐assembly fine‐tuning strategy is proposed to adjust the aggregated morphology of heptamethine cyanine (Cy7) dyes, the well‐known NIR dyes. Three hydrophilic Cy7 derivatives Cy‐nCOOH ( n = 1, 2, and 3) are synthesized, and then are coordinated with Cu 2+ to obtain different aggregates. Cy‐1COOH/Cu aggregates form partial J‐aggregates. Cy‐2COOH/Cu aggregates are amorphous. Noteworthily, Cy‐3COOH/Cu aggregates exhibit significant H‐type aggregation. Moreover, Cy‐3COOH/Cu aggregates show about threefold higher photothermal conversion efficiency and obviously enhanced photostability than Cy‐1COOH/Cu and Cy‐2COOH/Cu aggregates. It is demonstrated that H‐aggregates with face‐to‐face π–π stacking greatly quench fluorescence and inhibit singlet oxygen ( 1 O 2 ) production, which lead to the improved photothermal performances. In vitro and in vivo experiments demonstrate the remarkable tumor PTT efficiency of Cy‐3COOH/Cu H‐aggregates. This study provides a new insight into how to precisely control molecular aggregation of organic dyes in supramolecular self‐assembly for enhanced tumor phototherapy.