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

Abstract

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...

Improvement of Photodynamic Activity of Lipid–Membrane‐Incorporated Fullerene Derivative by Combination with a Photo‐Antenna Molecule

“…We investigated the levels of generated cytotoxic 1 O 2 by liposomal PS under visible‐light irradiation at a wavelength greater than 620 nm. We have reported that fullerenes and their derivatives transfer energy to 3 O 2 to give singlet oxygen molecules ( 1 O 2 ) (energy‐transfer pathway Type II) . The 1 O 2 generation ability was studied through the photoreaction between anthracene and 1 O 2 .…”

“…Although a lipid–membrane‐incorporating C 60 (LMIC 60 ) showed high photodynamic activity toward HeLa cells under photoirradiation between 350–500 nm, the light absorption of C 60 between 600–700 nm is too low to show photodynamic activity at wavelengths above 600 nm, which are the most suitable wavelengths for PDT. We have reported previously that a solution to this problem is the coexistence of light‐harvesting antenna molecules and pristine C 60 in lipid bilayers by a biomimetic approach of photosynthesis . The photodynamic activity of the dyad systems can be improved by suitable choice of fullerenes and/or antenna molecules.…”

Photodynamic Activity of Fullerene Derivatives Solubilized in Water by Natural‐Product‐Based Solubilizing Agents

“…As a third alternative method, we prepared LMIC 60 and LMIC 70 by using the exchange method by transferring fullerenes from two γ‐CDx cavities in the γ‐CDx ⋅ C 60 and γ‐CDx ⋅ C 70 complexes to the lipid membranes after heating (Scheme C) . Both ratios of [C 60 ]/[DMPC] and [C 70 ]/[DMPC] in the solutions of LMIC 60 and LMIC 70 obtained by using the exchange method (Figure ) were determined to be 30 mol %, and the values were 14 and 100 times larger, respectively, than those obtained by using the premixing method (2.3 and 0.3 mol %, respectively) .…”

“…As previously mentioned, a dyad system consisting of C 60 and DiD within the same liposome resolves the poor absorption of C 60 over the long‐wavelength range (600–700 nm) . However, because C 60 , which exists near the center of the membrane bilayer, as mentioned in Section 3.4, keeps DiD at a distance, the positions are not optimal for energy transfer between C 60 and DiD.…”

Fullerene derivatives as nano-additives in polymer composites

“…The antenna molecule can be included into lipid membrane bilayers together with fullerene C 60 molecules. 262 For additional information on the light-harvesting antenna systems, see Ref. 47.…”