Photodynamic therapy (PDT) is an emerging approach for the treatment of tumor diseases that has received growing interest in the past few years. In this study, we constructed liposomal photosensitizers (PS) for PDT by shoehorning as light-harvesting "antenna" molecules and dense [60]fullerene (C 60 ) into lipid membrane bilayers. The liposomal PS showed improved photodynamic activity toward human cancer cells via the photoenergy transfer from photoactivated antenna molecules to C 60 .KEYWORDS Energy transfer, fullerenes, photodynamic therapy, photosensitizers, liposomes P hotodynamic therapy (PDT) is a next-generation cancer treatment based on cytotoxic reactive oxygen species (ROS) producing photochemical reactions between photoexcited photosensitizers (PS) and molecular oxygen. 1,2 Due to the formation of a long-lived triplet state and the high photoproduction ability of ROS, fullerenes have attracted significant attention as PS of PDT. [3][4][5][6][7][8][9][10][11][12][13] We have previously reported that liposomal lipid membrane can be used for solubilization of unmodified [60]fullerenes (C 60 ) to overcome their poor water solubility. The produced cationic lipid membrane incorporating C 60 (LMIC 60 ) showed high cytotoxicity under light irradiation between 350-500 nm.10-13 However, from a practical application standpoint, the poor absorption of C 60 between 600 and 700 nm, which is the optimal wavelength range for PDT, remains problematic.In photosynthesis, solar energy is efficiently converted into chemical potential energy by highly organized multiprotein assemblies in the thylakoid membrane architecture of chloroplasts. In this process, photon energy is absorbed by the pigment antenna molecules and transferred to the reaction centers. The energy transfer model which occurs between pigment antenna molecules and the reaction centers represents an attractive approach to overcome the poor absorption of C 60 at long wavelengths. In this study, thylakoid membrane architecture mimetic liposomal PS of PDT were constructed by shoehorning light-harvesting "antenna" molecules and dense C 60 into lipid membrane bilayers (Figure 1). In this PS, photoenergy was absorbed by antenna molecules and transferred to C 60 to generate the ROS. To construct the liposomal PS, LMIC 60 is a convenient platform for placing antenna molecules and C 60 in close proximity because the antenna molecule-introduced liposome can be easily prepared through liposome staining using a lipid membrane probe. By employing liposomes, a direct covalent link between the antenna molecules and C 60 can be avoided, resulting in the efficient generation of ROS because unmodified fullerenes generate ROS more efficiently than other chemically modified C 60 derivatives. 14 1,1 0 -Dioctadecyl-3,3,3 0 ,3 0 -tetramethylindodicarbocyanine (DiD) molecules, dialkylated carbocyanine lipid membrane probes, were used as light-harvesting antenna molecules because dialkylated carbocyanine lipid membrane probes have no appreciable cytotoxicity, 15,16 and DiD m...