DNA Cleavage via Superoxide Anion Formed in Photoinduced Electron Transfer from NADH to γ-Cyclodextrin-Bicapped C<sub>60</sub> in an Oxygen-Saturated Aqueous Solution

Nakanishi, Ikuo; Fukuzumi, Shunichi; Konishi, Toshifumi; Ohkubo, Kei; Fujitsuka, Mamoru; Ito, Osamu; Miyata, Naoki

doi:10.1021/jp013215j

Cited by 78 publications

(69 citation statements)

References 82 publications

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“…22 These data clearly indicate that photon energy absorbed by DiD molecules is transferred to C 60 via an energy transfer mechanism and 1 O 2 was generated from C 60 ( Figure S6 in the Supporting Information).…”

Section: O 2 )mentioning

confidence: 78%

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

Ikeda

Akiyama

Ogawa

et al. 2010

ACS Med. Chem. Lett.

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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...

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Section: O 2 )mentioning

confidence: 78%

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

Ikeda

Akiyama

Ogawa

et al. 2010

ACS Med. Chem. Lett.

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“…18 The reduction of NBT with O 2 •− was not detected following the photoirradiation of the γ-CDx complexes of C 60 , 1, 2, and 3, although formazan was readily detected in the C 60 ·γ-CDx complex positive control samples in the presence of NADH ( Figure S5, Supporting Information). 30 These results indicate that O 2 •− is not generated by these complexes under the photoirradiation conditions. …”

mentioning

confidence: 85%

Cyclodextrin Complexed [60]Fullerene Derivatives with High Levels of Photodynamic Activity by Long Wavelength Excitation

Ikeda¹,

Iizuka²,

Maekubo³

et al. 2013

ACS Med. Chem. Lett.

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ABSTRACT:We have evaluated the photodynamic activities of C 60 derivative·γ-cyclodextrin (γ-CDx) complexes and demonstrated that they were significantly higher than those of the pristine C 60 and C 70 ·γ-CDx complexes under photoirradiation at long wavelengths (610−720 nm), which represent the optimal wavelengths for photodynamic therapy (PDT). In particular, the cationic C 60 derivative·γ-CDx complex had the highest photodynamic ability because the complex possessed the ability to generate high levels of 1 O 2 and provided a higher level of intracellular uptake. The photodynamic activity of this complex was greater than that of photofrin, which is the most widely used of the known clinical photosensitizers. These findings therefore provide a significant level of information toward the optimization of molecular design strategies for the synthesis of fullerene derivatives for PDT. KEYWORDS: Fullerenes, cyclodextrin, photodynamic therapy, photosensitizers W ater-solubilized fullerenes (C 60 and C 70 ) have recently been reported for their use as potential photosensitizers because C 60 and C 70 are efficient visible-light triplet-sensitizers with pronounced photoproduction abilities for the generation of reactive oxygen species (ROS).1 γ-Cyclodextrin (CDx)-complexed C 60 or C 70 can be isolated as independent units through γ-CDx inclusion in water, allowing for the selfquenching of photoexcited states to be avoided. 2−4 To improve the photoactivity of these fullerene·γ-CDx complexes, it is important that the fullerene or γ-CDx units are effectively functionalized. Furthermore, for pharmaceutical applications such as photodynamic therapy (PDT), improvements are required in a number of areas, including (i) the generation activity of ROS during the photoirradiation at longer wavelength with high biological tissue permeability; (ii) intracellular uptake; and (iii) the stability and solubility of the complexes. Unfortunately, however, the functionalization of fullerene or γ-CDx often results in a reduction in the overall stability of the complex.3,5 In a recent publication, we reported that several functionalized C 60 derivatives, such as the Nmethylpyrrolidine, N,N-dimethylpyrrolidinium, and N-acetylpyrrolidine derivatives (1−3, Figure 1) of C 60 , could form stable complexes with γ-CDx using a mechanochemical highspeed vibration milling apparatus according to Komatsu's method. 3,6,7 The γ-CDx-complexed C 60 derivatives of 1−3 were found to be soluble in water at high concentrations (i.e., >1.0 mM), with solubility levels comparable to that of unmodified C 60 (2.2 mM).6,7 These complexes possessed a 1:2 stoichiometry of the γ-CDx unit to the C 60 derivative and existed in a [2]pseudorotaxane conformation. 7Herein, we report a comparison of the photodynamic activities of γ-CDx-complexed C 60 derivatives containing three different nitrogen atom-containing groups, including amino, ammonium, and amide groups. The photodynamic activities of the γ-CDx-complexed C 60 derivatives toward human cervical cancer HeLa cells were e...

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“…Our previous studies (10) have shown that a variety of watersoluble fullerenes can efficiently generate singlet oxygen ( 1 O 2 ) upon irradiation via energy transfer (type II photochemical mechanism) from the excited triplet of fullerene to oxygen (11)(12)(13). There are also reports that photoirradiation of fullerenes in aqueous systems results in the production of the corresponding radical anions (C 60 ·-) followed by generation of superoxide (O 2 ·-) and hydroxyl radical ( · OH) via electron transfer (type I photochemical mechanism), especially in the presence of electron donors (such as NADH or amines) (14)(15)(16)(17)(18). These two photochemical mechanisms, typically present during photodynamic therapy (PDT), constitute the main pathways for the photoinduced toxicity of fullerenes (19).…”

Section: Introductionmentioning

confidence: 99%

Pristine (C₆₀) and Hydroxylated [C₆₀(OH)₂₄] Fullerene Phototoxicity towards HaCaT Keratinocytes: Type I vs Type II Mechanisms

Zhao

Bilski

et al. 2008

Chem. Res. Toxicol.

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The increasing use of fullerene nanomaterials has prompted widespread concern over their biological effects. Herein, we have studied the phototoxicity of γ-cyclodextrin bicapped pristine C 60 [(γ-CyD) 2 /C 60 ] and its water-soluble derivative C 60 (OH) 24 toward human keratinocytes. Our results demonstrated that irradiation of (γ-CyD) 2 /C 60 or C 60 (OH) 24 in D 2 O generated singlet oxygen with quantum yields of 0.76 and 0.08, respectively. Irradiation (>400 nm) of C 60 (OH) 24 generated superoxide as detected by the EPR spin trapping technique; superoxide generation was enhanced by addition of the electron donor nicotinamide adenine dinucleotide (reduced) (NADH). During the irradiation of (γ-CyD) 2 /C 60 , superoxide was generated only in the presence of NADH. Cell viability measurements demonstrated that (γ-CyD) 2 /C 60 was about 60 times more phototoxic to human keratinocytes than C 60 (OH) 24 . UVA irradiation of human keratinocytes in the presence of (γ-CyD) 2 /C 60 resulted in a significant rise in intracellular protein-derived peroxides, suggesting a type II mechanism for phototoxicity. UVA irradiation of human keratinocytes in the presence of C 60 (OH) 24 produced diffuse intracellular fluorescence when the hydrogen peroxide probe Peroxyfluor-1 was present, suggesting a type I mechanism. Our results clearly show that the phototoxicity induced by (γ-CyD) 2 /C 60 is mainly mediated by singlet oxygen with a minor contribution from superoxide, while C 60 (OH) 24 phototoxicity is mainly due to superoxide.

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DNA Cleavage via Superoxide Anion Formed in Photoinduced Electron Transfer from NADH to γ-Cyclodextrin-Bicapped C₆₀ in an Oxygen-Saturated Aqueous Solution

Cited by 78 publications

References 82 publications

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

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

Cyclodextrin Complexed [60]Fullerene Derivatives with High Levels of Photodynamic Activity by Long Wavelength Excitation

Pristine (C₆₀) and Hydroxylated [C₆₀(OH)₂₄] Fullerene Phototoxicity towards HaCaT Keratinocytes: Type I vs Type II Mechanisms

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DNA Cleavage via Superoxide Anion Formed in Photoinduced Electron Transfer from NADH to γ-Cyclodextrin-Bicapped C60 in an Oxygen-Saturated Aqueous Solution

Cited by 78 publications

References 82 publications

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

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

Cyclodextrin Complexed [60]Fullerene Derivatives with High Levels of Photodynamic Activity by Long Wavelength Excitation

Pristine (C60) and Hydroxylated [C60(OH)24] Fullerene Phototoxicity towards HaCaT Keratinocytes: Type I vs Type II Mechanisms

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DNA Cleavage via Superoxide Anion Formed in Photoinduced Electron Transfer from NADH to γ-Cyclodextrin-Bicapped C₆₀ in an Oxygen-Saturated Aqueous Solution

Pristine (C₆₀) and Hydroxylated [C₆₀(OH)₂₄] Fullerene Phototoxicity towards HaCaT Keratinocytes: Type I vs Type II Mechanisms