title: Sugar and heavy atom effects of glycoconjugated chlorin palladium complex on photocytotoxicity.
abstract: Palladium(II) complexes of glycoconjugated porphyrin and pyrrolidine-fused chlorin were prepared to examine sugar and heavy atom effects on in vitro photocytotoxicity. Cellular uptake into HeLa cells was enhanced by introducing sugar units regardless of other features, such as the central ion (free base or palladium(II) ion) and the ring structure (porphyrin or chlorin). The palladium(II) complex of glycoconjugated pyrrolidine-fused chlorin (PdPC2) exerted an excellent degree of photocytotoxicity not only on HeLa cells, but also on metastatic B16-BL6 cells, weakly metastatic B16F1 cells, and metastatic 4T1 cells. However, free-base glycoconjugated pyrrolidine-fused chlorin (PC2) also exerted similar or much higher photocytotoxicity rather than PdPC2. Therefore, the palladium(II) ion did not improve the in vitro photocytotoxicity of PC2. The enhanced singlet oxygen generation of palladium(II) complexes (i.e., the heavy atom effect) was confirmed at least in O(2)-saturated D(2)O. In addition, the formation of hydrogen peroxide and hydroxyl radical were also detected in O(2)-saturated phosphate buffered saline. However, the reactive oxygen species (ROS) generation efficiency, which is the product of the (relative) quantum yield of each ROS and the light absorbing ability, did not fit the trends of photocytotoxicity seen for the photosensitizers. In our glycoconjugated photosensitizers tested, the best indicator of the photocytotoxicity was found to be the light absorbing ability (namely, the oscillator strength in the wavelength region applied in the photocytotoxicity test). These results indicated that photochemical characteristics of glycoconjugated photosensitizers were notably susceptible to the microenvironment. The biological characteristics, such as the sugar effect, were a much more reliable approach to improving the photocytotoxicity of photosensitizers.
authors.affiliation: Department of Chemical and Biological Engineering, Ube National College of Technology , 2-14-1 Tokiwadai, Ube 755-8555, Japan. hirohara@ube-k.ac.jp
authors.forename: Shiho
authors.initials: S
authors.lastname: Hirohara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Ryota
authors.initials: R
authors.lastname: Funasako
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Yasui
authors.forename: Masayasu
authors.initials: M
authors.lastname: Totani
authors.forename: Hiroki
authors.initials: H
authors.lastname: Alitomo
authors.forename: Junpei
authors.initials: J
authors.lastname: Yuasa
authors.forename: Tuyoshi
authors.initials: T
authors.lastname: Kawai
authors.forename: Chio
authors.initials: C
authors.lastname: Oka
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawaichi
authors.forename: Makoto
authors.initials: M
authors.lastname: Obata
authors.forename: Masao
authors.initials: M
authors.lastname: Tanihara
mesh_terms: D002241:Carbohydrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D006001:Glycoconjugates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002241:Carbohydrates; D006001:Glycoconjugates; D011166:Porphyrins; D017382:Reactive Oxygen Species; C006969:chlorin; D010165:Palladium