Putting a “C60 Ball” and Chain to Chlorin e6 Improves Its Cellular Uptake and Photodynamic Performances

Abstract

Chlorin e6 (Ce6) and fullerene (C60) are among the most used photosensitizers (PSs) for photodynamic therapy (PDT). Through the combination of the chemical and photophysical properties of Ce6 and C60, in principle, we can obtain an “ideal” photosensitizer that is able to bypass the limitations of the two molecules alone, i.e., the low cellular uptake of Ce6 and the scarce solubility and absorption in the red region of the C60. Here, we synthesized and characterized a Ce6–C60 dyad. The UV-Vis spectrum of the dyad showed the typical absorption bands of both fullerene and Ce6, while a quenching of Ce6 fluorescence was observed. This behavior is typical in the formation of a fullerene–antenna system and is due to the intramolecular energy, or electron transfer from the antenna (Ce6) to the fullerene. Consequently, the Ce6–C60 dyad showed an enhancement in the generation of reactive oxygen species (ROS). Flow cytometry measurements demonstrated how the uptake of the Ce6 was strongly improved by the conjugation with C60. The Ce6–C60 dyad exhibited in A431 cancer cells low dark toxicity and a higher PDT efficacy than Ce6 alone, due to the enhancement of the uptake and the improvement of ROS generation.