Control of photobleaching in photodynamic therapy using the photodecarbonylation reaction of ruthenium phthalocyanine complexes via stepwise two-photon excitation.
In this study, we have investigated the photochemical properties and photodynamic effects of ruthenium phthalocyanine (RuPc(CO)(Py)) and naphthalocyanine (RuNc(CO)(Py)) complexes. When a nanosecond-pulsed laser is used, the photodecarbonylation of our Ru complexes efficiently proceeds via stepwise two-photon excitation, while the reaction yields are negligibly small when a continuous-wave (CW) laser is employed. The pulsed laser selective photodecarbonylation decreases the Q-band absorbance, which satisfies what the photodynamic therapy (PDT) requires of the photobleaching. For RuPc(CO)(Py), the photochemical reactions including both the photodecarbonylation and just photobleaching occur in HeLa cells in vitro. Toxicity and phototoxicity tests indicate that our RuPc(CO)(Py) and RuNc(CO)(Py) complexes in concentrations of 0.3-1 microM and 1-2 microM, respectively, are applicable as PDT agents. The phototoxicity is consistent with the photochemical properties of these complexes, namely, excited triplet lifetimes (10 and 4.8 micros for the Pc and Nc complexes, respectively) and singlet oxygen yields (0.48 and 0.35 for the Pc and Nc complexes, respectively). On the basis of these results, we propose a novel concept for achieving a greater depth of necrosis in PDT as follows: (1) PDT of upper cellular layers using CW-laser irradiation; (2) efficient photobleaching in upper cellular layers using pulsed dye-laser irradiation, which results in an increase in the therapeutic depth of red light; (3) PDT directed toward deeper tumor tissues using CW laser irradiation. In addition, these Ru complexes are promising as CO release agents for investigative biochemistry.
Ishii
Kazuyuki
K
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba Meguro-ku, Tokyo, Japan. k-ishii@iis.u-tokyo.ac.jp
Shiine
Masahiko
M
Shimizu
Yoshitaka
Y
Hoshino
Shun-ichi
S
Abe
Hisaku
H
Sogawa
Kazuhiro
K
Kobayashi
Nagao
N
D002255:Carbonic Acid / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D038761:Photobleaching; D010778:Photochemotherapy; D017785:Photons; D013053:Spectrophotometry
D009942:Organometallic Compounds; C528283:ruthenium phthalocyanine; D002255:Carbonic Acid