Premium
Silylation Improves the Photodynamic Activity of Tetraphenylporphyrin Derivatives In Vitro and In Vivo
Author(s) -
Horiuchi Hiroaki,
Hosaka Masahiro,
Mashio Hiroyuki,
Terata Motoki,
Ishida Shintaro,
Kyushin Soichiro,
Okutsu Tetsuo,
Takeuchi Toshiyuki,
Hiratsuka Hiroshi
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303120
Subject(s) - photodynamic therapy , silylation , tetraphenylporphyrin , photosensitizer , in vivo , singlet oxygen , porphyrin , chemistry , in vitro , photochemistry , derivative (finance) , selectivity , sensitization , biochemistry , catalysis , oxygen , organic chemistry , medicine , biology , immunology , microbiology and biotechnology , financial economics , economics
The effects of silyl and hydrophilic groups on the photodynamic properties of tetraphenylporphyrin (TPP) derivatives have been studied in vitro and in vivo. Silylation led to an improvement in the quantum yield of singlet oxygen sensitization for both sulfo and carboxy derivatives, although the silylation did not affect other photophysical properties. Silylation also improved the cellular uptake efficiency for both sulfo and carboxy derivatives, enhancing the in vitro photodynamic activity of the photosensitizer in U251 human glioma cells. The carboxy derivative (SiTPPC 4 ) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS 4 ), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC 4 was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC 4 in tumors was 13 times higher than that in muscle 12 h after drug administration. We also studied tumor response after treatment and found that silylation enhanced in vivo photodynamic activity significantly. SiTPPC 4 shows higher photodynamic activity than NPe6 with white light irradiation.