Highly aqueously stable C₆₀-polymer nanoparticles with excellent photodynamic property for potential cancer treatment

Fullerenes are a class of carbon nanomaterials that find a wide range of applications in biomedical fields, especially for photodynamic cancer therapy because of its photosensitive effect. However, hydrophobic fullerenes can only be dispersed in organic solvents which hinders their biomedical applications. Here, we report a facile method to prepare highly water-dispersible fullerene (C₆₀)-polymer nanoparticles with hydrodynamic sizes of 50-70 nm. Hydrophilic random copolymers containing different ratios of polyethylene glycol methyl ether methacrylate and 2-aminoethylmethacrylamide were synthesized for conjugating with C₆₀ molecules through efficient nucleophilic Michael addition reaction between amine groups from hydrophilic polymer and carbon-carbon double bonds from C₆₀. As a result, the amphiphilic C₆₀-polymer conjugates could be well dispersed and nano-assembled in water with a C₆₀ concentration as high as 7.8 mg/mL, demonstrating a significant improvement for the solubility of C₆₀ in an aqueous system. Owing to the high C₆₀ content, the C₆₀-polymer nanoparticles showed a strong photodynamic therapy effect on human lung cancer cells (A549) under light irradiation (450 nm) in both 2D cell culture and 3D spheroid culture, while demonstrating ignorable cytotoxicity under dark. This highly efficient and convenient method to prepare water-dispersible C₆₀-polymer conjugates may have a great impact on the future biomedical applications of fullerenes.