One-pot accessing of meso-Aryl heptamethine indocyanine NIR fluorophores and potential application in developing dye-antibody conjugate for imaging tumor

In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso-Aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones with various aromatic lithium (ArLi), followed by acidification, could straightforwardly give rise to the products in one-pot way. Importantly, due to the strong nucleophilicity of ArLi, a series of bulky hydrophilic aromatic groups can be facilely integrated into the meso-position of heptamethine indocyanines, not only effectively inhibiting the undesired dye self-aggregation but also largely improving the water-solubility. Using one of anti-aggregation meso-Aryl heptamethine indocyanines, we fabricated a dye-antibody conjugate for in vivo imaging tumor in a mouse model and achieved a high tumor-to-normal tissue ratio. The work laid a chemical foundation for constructing various meso-Aryl heptamethine indocyanines, facilitating the advanced imaging and therapeutic applications in future.