The
photodynamic therapy (
PDT) activity of the
bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine (
SiNc 8) was evaluated against the EMT-6
tumor implanted intradermally in BALB/c mice. The
SiNc 8 was formulated in aqueous
emulsions based on
Cremophor EL or
Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacokinetics. Compared to
Cremophor, Solutol promoted rapid plasma clearance and high liver retention of the
dye, combined with a slight increase of
dye tumor concentrations. The
PDT action spectrum for
tumor response of
SiNc 8 in
Cremophor (190 mW cm-2, 200 J cm-2, 24 h postinjection [p.i.] of 1 mumol kg-1) showed a maximum at 780 nm, which corresponds to the absorption maximum of the monomeric
dye as well as the in vivo maximum change in the "diffuse optical density" produced by the
dye. The extent of
tumor necrosis increased with augmented
dye and light doses. Regardless of the formulation, at 1 h p.i. of 0.1 mumol kg-1
SiNc 8,
PDT efficiency (190 mW cm-2, 400 J cm-2) was high but accompanied by severe damage to normal tissues, at 24 h p.i.
PDT resulted in complete
tumor regression in 80% of the animals without adverse effects to adjacent tissues, while at 72 h p.i.
PDT induced no
tumor response with
Cremophor and only a partial response with Solutol. At the latter time point, plasma
dye clearance was nearly complete while
tumor tissue levels remained high, suggesting that
tumor response correlates with plasma rather than
tumor dye levels. Skin sensitivity of SKhI mice to solar-simulated radiation was lower with
SiNc 8 as compared to
Photofrin. Our data suggest the potential of
SiNc 8 as a far-red absorbing
photosensitizer in clinical
PDT.