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...

X-Ray crystallography revealed that the C(60) derivative·γ-cyclodextrin (γ-CDx) complex has a pseudorotaxane structure and the structure of the crystal clarified the importance of multi-point hydrogen bonds between two γ-CDxs for stabilising the 3·γ-CDx complex.

Anionic and neutral fullerene derivatives were dissolved in water by using β-(1,3-1,6)-d-glucan (β-1,3-glucan) as a solubilizing agent. In the water-solubilized complexes, the concentrations of fullerene derivatives were ≈0.30 mm and the average particle sizes were ≈90 nm. The β-1,3-glucan-complexed fullerene derivative with a carboxylic acid was found to have higher photodynamic activity toward macrophages under visible-light irradiation (λ>610 nm) than other β-1,3-glucan-complexed fullerene derivatives. This result suggests that carboxylic acid moieties in the complex enhance the binding affinity with β-1,3-glucan receptors on the surface of macrophages when the β-1,3-glucan is recognized. In contrast, all β-1,3-glucan-complexed fullerene derivatives showed no photodynamic activity toward HeLa cells under the same conditions.

Pyrrolidine and N,N-dimethylpyrrolidinium derivatives of C60 could be solubilized in water with the aid of γ-cyclodextrin. The complexes were found to be soluble in water at high concentrations over 1.5 mM. These solubility values are significantly higher than those of other C60 derivatives reported previously. Furthermore, these solutions are stable for at least one month at room temperature.

A fullerene derivative bearing a carboxylic acid was dissolved in water by formation of a globular structure, which looks like the bamboo work in the picture, using β‐1,3‐glucan as a solubilizing agent. The complex has a high photodynamic activity toward macrophages under visible‐light irradiation, because the carboxylic acid moieties in the complex enhance the binding affinity with β‐1,3‐glucan‐receptors on the macrophage surface. More information can be found in the Full Paper by Atsushi Ikeda et al. on page 1069 in Issue 10, 2017 (DOI: 10.1002/asia.201700182.).