Silylation improves the photodynamic activity of tetraphenylporphyrin derivatives in vitro and in vivo

Hiroaki Horiuchi, Masahiro Hosaka, Hiroyuki Mashio, Motoki Terata, Shintaro Ishida, Soichiro Kyushin, Tetsuo Okutsu, Toshiyuki Takeuchi, Hiroshi Hiratsuka

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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 (SiTPPC4) was found to show higher cellular uptake efficiency and in vitro photodynamic activity than the corresponding sulfo derivative (SiTPPS4), which indicates that the carboxy group is a more promising hydrophilic group than the sulfo group in the silylated porphyrin. SiTPPC4 was found to show high selective accumulation efficiency in tumors, although almost no tumor selectivity was observed for the nonsilylated porphyrin. The concentration of SiTPPC4 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. Improved photosensitizers: Silylation improves the quantum yield of singlet oxygen sensitization, cellular uptake efficiency, and selective accumulation efficiency in tumors. As a result of these improvements, silylation significantly enhances photodynamic activity (see figure). The results of this work suggest that silylation is a promising strategy for improving photosensitizers for photodynamic therapy.

Original languageEnglish
Pages (from-to)6054-6060
Number of pages7
JournalChemistry - A European Journal
Volume20
Issue number20
DOIs
Publication statusPublished - 2014 May 12

Keywords

  • biological activity
  • fluorescence
  • photodynamic therapy
  • porphyrinoids
  • silylation

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