Soluble Nanographene C₂₂₂: Synthesis and Applications for Synergistic Photodynamic/Photothermal Therapy

Nanographene C₂₂₂, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C₂₂₂ difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C₂₂₂ with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C₂₂₂. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C₂₂₂ to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C₂₂₂ core, the resulting water-soluble C₂₂₂ emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.