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A. Ikeda, K. Ashizawa, Y. Tsuchiya, M. Ueda, K. Sugikawa, Formation of lipid membrane-incorporated small π-molecules bearing hydrophilic groups, RSC Adv., 6 (82), 78505–78513 (2016). (DOI: 10.1039/c6ra18635a)
19種類の有機π分子含有リポソームを作成し、その安定性を評価した。その結果、(i) 安定な有機π分子含有リポソームを形成するもの、(ii) 有機π分子が沈殿するもの、(iii) 有機π分子含有リポソームが不安定化し小さなリポソームもしくはミセルになるもの、(iv) バルク水溶液中に有機π分子が漏れ出すもの、の四つに分類できることがわかった。
Nineteen π-conjugated molecules were evaluated in terms of their ability to be stably incorporated into lipid membranes. The resulting lipid membrane-incorporated π-conjugated guest molecules (LMIGs) were classified into four categories, including (i) those that formed stable LMIGs; (ii) those where some of guest molecules precipitated; (iii) those that formed small self-aggregates consisting of lipids and/or guest molecules; and (iv) those that leaked some of the guest molecules into the bulk water.


K. Sugikawa, K. Kozawa, M. Ueda, A. Ikeda, Size Controlled Fullerene Nanoparticles Prepared by Guest Exchange of γ-Cyclodextrin Complexes in Water, RSC Adv., 6 (78), 74696–74699 (2016). (DOI: 10.1039/c6ra16513c)
Water-dispersible fullerene nanoparticles were prepared by guest exchange of fullerene–γ- cyclodextrin complexes with polyethylene glycol in water. The fullerenes expelled from the γ-cyclodextrin cavity immediately aggregate into nanoparticles that are stable in water. The size and morphology of the nanoparticles could easily be controlled by changing the initial concentration of the complex.


A. Ikeda, R. Funada, K. Sugikawa, Different Stabilities of Liposomes Containing Saturated and Unsaturated Lipids toward the Addition of Cyclodextrins, Org. Biomol. Chem., 14 (22), 5065–5072 (2016). (DOI: 10.1039/C6OB00535G)
We show that liposomes composed of unsaturated lipids are more stable than those composed of saturated lipids toward DMe-β-CDx DMe-α-CDx and DMe-β-CDx. The Hill coefficient values (n) indicated that the saturated lipid•DMe-CDx complexes had stoichiometric ratios in the range of 1:3‒1:4, while the unsaturated lipid•DMe-CDx complexes had ratios in the range of 1:1.5‒1:3. That is, a cis alkene group in the unsaturated lipids prevented complexation with a second DMe-CDx in the direction of the acyl chain.


A. Narumi, T. Tsuji, K. Shinohara, H. Yamazaki, M. Kikuchi, S. Kawaguchi, T. Mae, A. Ikeda, Y. Sakai, H. Kataoka, A. Inoue, A. Nomoto, J. Kikuchi, S. Yano, Maltotriose-Conjugation to Fluorinated Chlorin Derivative Generating PDT Photosensitizer with Improved Water-Solubility, Org. Biomol. Chem., 14 (14), 3608–3613 (2016). (DOI: 10.1039/C6OB00276E)
A chlorin conjugated with four maltotriose moieties was soluble in water. The chlorin derivative showed an excellent biocompatibility, strong photoabsorption in the longer wavelength regions, and a very high photocytotoxicity compared with the porphyrin derivatives.


K. Sugikawa, T. Kadota, K. Yasuhara, A. Ikeda, Anisotropic Self-Assembly of Citrate-Coated Gold Nanoparticles on Fluidic Liposomes, Angew. Chem. Int. Ed., 55 (12), 4059–4063 (2016). (DOI:10.1002/anie.201511785)
クエン酸で保護されたアニオン性金ナノ粒子は双性イオン型脂質二分子膜 (リポソーム) の表面に吸着する。吸着した金ナノ粒子は脂質二分子膜の相転移温度以下では孤立分散状態にあるが、相転移温度以上では一次元に組織化した。
Liposomes decorated with gold nanoparticles (AuNPs) were prepared to investigate the assembly manner of AuNPs on the surface of lipid membrane. The adsorbed AuNPs were fixed on the liposome surfaces and did not form an assembled structure below the liposome phase transition temperature (Tm). In contrast, anisotropic assembly of the cAuNPs was observed upon heating the composite solution above Tm, in which the phospholipids are fluid.


K. Sugikawa, A. Kubo, A. Ikeda, pH-Responsive Nanogels Containing Fullerenes: Synthesis via a Fullerene Exchange Method and Photoactivity, Chem. Lett., 45 (1), 60–62, (2016). (DOI:10.1246/cl.150924)
Fullerenes solubilized by γ-cyclodextrins are efficiently transferred to only the swollen state of the nanogel networks, i.e., below a critical swelling pH. The synthesized fullerene-incorporated pH-responsive nanogels efficiently generate activated oxygen (1O2) in a pH-responsive manner when irradiated, indicating their potential for use as PDT photosensitizers. We believe that these findings are critical to the development of fullerene-based PDT applications.


A. Ikeda, S. Hino, T. Mae, Y. Tsuchiya, K. Sugikawa, M. Tsukamoto, K. Yasuhara, H. Shigeto, H. Funabashi, A. Kuroda, M. Akiyama, Porphyrin-uptake in Liposomes and Living Cells Using an Exchange Method with Cyclodextrin, RSC Advances, 5 (127), 105279–105287 (2015). (DOI: 10.1039/C5RA24985F)
It is currently not possible to achieve the incorporation of tetraphenylporphyrin (TPP) into a lipid membrane using conventional methods, such as the premixing and the ethanol injection methods. In this study, we have succeeded in the preparation of lipid-membrane-incorporated TPP with a high concentration of TPP using the exchange method for the transfer of TPP from TPP•cyclodextrin complexes to liposomes as well as living cells.


S. Yano, M. Naemura, A. Toshimitsu, M. Akiyama, A. Ikeda, J. Kikuchi, X. Shen, Q. Duan, A. Narumi, M. Inoue, K. Ohkubo, S. Fukuzum, Efficient Singlet Oxygen Generation from Sugar Pendant C60 Derivatives for Photodynamic Therapy, Chem. Commun., 51 (93), 16605−16608 (2015). (DOI: 10.1039/C5CC07353G)
The water-soluble glucose-pendant C60 compound, exhibited high photocytotoxicity toward HeLa cells due to the more efficient singlet oxygen generation as compared with that of glucose-pendant azafulleroids.


A. Ikeda, N. Iwata, S. Hino, T. Mae, Y. Tsuchiya, K. Sugikawa, T. Hirao, T. Haino, K. Ohara, K. Yamaguchi, Liposome Collapse Resulting from an Allosteric Interaction between 2,6-Dimethyl-β-cyclodextrins and Lipids, RSC Advances, 5 (95), 77746−77754 (2015). (DOI: 10.1039/C5RA14970C)
It has been reported that heptakis(2,6-di-O-methyl)-β-cyclodextrin (DMe-β-CDx) exhibits higher levels of toxicity than many other CDxs. The higher toxicity of DMe-β-CDx has been attributed not only to its ability to affect the extraction of cholesterol from cell membrane but also to its ability to interact with lipids. In this study, we have shown that DMe-β-CDx possess the ability to affect the collapse of liposomes. It is noteworthy that these interactions between the lipids and DMe-β-CDx were positive allosterism.


A. Ikeda, S. Hino, K. Ashizawa, K. Sugikawa, J. Kikuchi, M. Tsukamoto, K. Yasuhara, Lipid-Membrane-Incorporated Hydrophobic Photochromic Molecules Prepared by the Exchange Method Using Cyclodextrins, Org. Biomol. Chem., 13 (22), 6175−6182 (2015). (DOI: 10.1039/C5OB00240K)
We succeeded in producing lipid-membrane-incorporated hydrophobic π-molecules, such as azobenzene (1) and stilbene (2) (LMI1 and LMI2), by the exchange method with a high ratio of [1 or 2]/[lipid] (20 mol%). Advantages of the exchange method are that (i) the long-term stabilities of LMI1 solutions prepared by the exchange method were much higher than those prepared by the classical, premixing method and (ii) the maximum ratio (20 mol%) of LMI2 obtained by the exchange method was two times higher than that obtained by the premixing method.