Quaternized microcrystalline cellulose as a surface-engineered polysaccharide carrier for regulating ICG aggregates and enhancing multimodal phototherapy.

Sustainable polysaccharide-based carriers offer a promising route to overcome the instability and aggregation issues of indocyanine green (ICG), a clinically approved phototherapy dye. In this study, a scalable approach is presented to construct quaternized microcrystalline cellulose (QMCC) carriers with tunable surface charge for stabilized and high-capacity ICG loading. By modulating the degree of quaternary ammonium substitution, QMCC effectively modulated ICG aggregation behavior, promoting the formation of broadened and red-shifted near-infrared absorption bands with enhanced photostability. Among them, QMCC2-ICG exhibited a balanced electrostatic and steric environment through the π-π stacking interaction, favoring the formation of hybrid aggregates with broad-spectrum absorption profiles and superior optical stability. This enabled high ICG loading (388.3 mg/g), elevated photothermal conversion efficiency (55.0 %), and robust singlet oxygen generation. 4 T1 in vitro experiments demonstrated improved cell phototoxicity, ROS-mediated cytotoxicity, and tumor cell migration inhibition. In vivo, QMCC2-ICG also showed excellent hemocompatibility and enabled strong photoacoustic imaging and tumor ablation in 4 T1-bearing mice. Histological and molecular assays confirmed apoptosis induction, proliferation inhibition, and biosafety. This work presents a sustainable polysaccharide platform that enables aggregation-state control and excited-state tuning for improved multimodal phototherapy, highlighting the role of surface charge and morphology in driving green therapeutic material design.