Intracellular Uptake and Photodynamic Activity of Water‐Soluble [60]‐ and [70]Fullerenes Incorporated in Liposomes

Abstract

Water-soluble fullerenes have attracted attention as promising compounds that have been used to forge new paths in the field of photo-biochemistry. To prepare water-soluble fullerenes, we employed lipid-membrane-incorporated fullerenes (LMICx; x=60 or 70) by using the fullerene exchange method from a gamma-cyclodextrin (gamma-CD) cavity to vesicles. LMIC60 have low toxicity in the dark and engender cell death by photoirradiation (lambda>350 nm). Furthermore, the photodynamic activity of LMIC70 is 4.7-fold that of LMIC60 for the same photon flux (lambda>400 nm). One of the reasons for the higher phototoxicity of LMIC70 is the higher generation of singlet oxygen (1O2) in LMIC70 than in LMIC60. The difference between LMIC60 and LMIC70 is considered to be simply derived from the amount of light absorption in the 400-700 nm region that is suitable for photodynamic therapy (PDT). To the best of our knowledge, this is the first case in which biological activity of C70 and its derivatives toward HeLa cells has been assayed.

Nanodrug applications in photodynamic therapy

“…For example, lipid membrane incorporated fullerenes were prepared via the fullerene exchange method from -cyclodextrin and showed low toxicity in the dark and good activity against HeLa cells after irradition. Notably, the C 70 derivatives showed a higher photodynamic activity then the C 60 derivatives [134]. Related surface cross-linked liposomes (cerasomes) also exhibit significant potential for PDT [135].…”

Photodynamic Activity of Liposomal Photosensitizers via Energy Transfer from Antenna Molecules to [60]Fullerene

“…Light-harvesting liposomes of LMIC 60 -DiD were prepared via fullerene exchange from the γ-cyclodextrin (γ-CDx) cavity to DiD contained liposomes (liposome-DiD) following a previously reported method. [10][11][12][13] Due to the efficient intracellular uptake of liposomes by tumor cells in our previously reports, liposomes with cationic surfaces were used for the preparation of LMIC 60 -DiD. 10,11 The structures of DiD and lipids are shown in Figure S1 in the Supporting Information.…”

“…13,19 APA is converted to endoperoxide form by the reaction with •-is detected as an increase of the absorption at 560 nm ( Figure S7b in the Supporting Information). The decrease of APA absorption was monitored as a function of time after irradiating samples.…”

“…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.…”

“…The produced cationic lipid membrane incorporating C 60 (LMIC 60 ) showed high cytotoxicity under light irradiation between 350-500 nm. [10][11][12][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.…”