ABSTRACT
The weak absorbance of pristine C60 , C70 , and fullerene derivatives at wavelengths over 600â nm hampers the use of these molecules as photosensitizers (PSs) for photodynamic therapy (PDT). The coexistence of light-harvesting antenna molecules with a fullerene derivative in lipid membrane bilayers solved this issue. By controlling the location of the C60 derivative in the lipid membrane, the liposomal dyad system for PDT improved the photodynamic activity via an efficient photoenergy transfer from antenna molecules to the fullerene derivative. The photodynamic activity was found to be much higher than those of dyad systems using pristine C60 and C70 .
Subject(s)
Fullerenes/chemistry , Lipid Bilayers/chemistry , Liposomes/chemistry , Photosensitizing Agents , PhotochemotherapyABSTRACT
Water-soluble cyclodextrin (CyD) complexed with porphyrin derivatives with different substituents in the meso-positions showed different photodynamic activities toward cancer cells under illumination at wavelengths over 600 nm, the most suitable wavelengths for photodynamic therapy (PDT). In particular, aniline- and phenol-substituted derivatives had high photodynamic activity because of the efficient intracellular uptake of the complexes by tumor cells. These complexes showed greater photodynamic activity than photofrin, currently the main drug in clinical use as a photosensitizer. These results represent a significant step toward the optimization of porphyrin derivatives as photosensitizers.
ABSTRACT
[60]Fullerene (C60) derivatives were incorporated into liposomes using a fullerene exchange method involving the transfer of the fullerene from the cavity of two γ-cyclodextrin molecules to a liposome. A lipid-membrane-incorporated C60 derivative bearing a polar group showed much higher photodynamic activity than the analogous system incorporating pristine C60.
Subject(s)
Fullerenes/chemistry , Fullerenes/pharmacology , Photochemotherapy , Cell Death/drug effects , Dose-Response Relationship, Drug , Fullerenes/administration & dosage , HeLa Cells , Humans , Liposomes , Molecular Structure , gamma-Cyclodextrins/administration & dosage , gamma-Cyclodextrins/chemistry , gamma-Cyclodextrins/pharmacologyABSTRACT
Photoactive molecules with the frameworks of chlorin and/or porphyrin possessing four perfluorinated aromatic rings were conjugated with maltotriose (Mal3) via the nucleophilic aromatic substitution reaction and subsequent deprotection reaction of the oligosaccharide moieties. The resulting oligosaccharide-conjugated molecules are ultimately improved as compared to the previously reported monosaccharide-counterparts in terms of water-solubility. In particular, a water-soluble chlorin derivative surrounded by four Mal3 molecules showed an excellent biocompatibility, strong photoabsorption in the longer wavelength regions, and a very high photocytotoxicity. Thus, the present synthetic route combined with the use of an oligosaccharide was shown to be a straightforward strategy to develop a third generation photosensitizer for photodynamic therapy (PDT).
