Pharmacokinetic and phototherapeutic properties of axially substituted Si(IV)-tetradibenzobarreleno-octabutoxyphthalocyanines.
Three Si(IV)-tetradibenzobarreleno-octabutoxyphthalocyanines (TDiBOPcs) bearing different axial ligands on the metal ion were studied for their tumour-localizing and-photosensitizing properties after i.v. injection via a Cremophor emulsion (0.35 mumol kg-1 b.w.) to Balb/c mice bearing an intramuscularly implanted MS-2 fibrosarcoma. In all cases, the maximum tumour accumulation of the photosensitizer (0.8-1.9 nmol g-1 of tissue) was found at 24 h after injection. The efficiency and selectivity of tumour targeting appeared to be dependent on the nature of the axial ligands; optimal values of these parameters were obtained in the case of the bis(trihexyl-siloxy)-substituted Si(IV)-TDiBOPc, which gave a 7-9 tumour/muscle ratio of phthalocyanine concentration at 24-48 h after injection. The extent of tumour response to PDT treatment was correlated with the concentration of the photosensitizer in the tumour tissue: upon 740 nm irradiation (180 mW cm-2, 200 J cm-2) at 48 h after injection of 0.35 mumol kg-1 of Si(IV)-TDiBOPc-C6H13, the tumour growth exhibited a delay of about 7 days.
Soncin
M
M
Department of Biology, University of Padova, Italy. polo@civ.bio.unipd.it
Busetti
A
A
Reddi
E
E
Jori
G
G
Rither
B D
BD
Kenney
M E
ME
Rodgers
M A
MA
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010789:Phototherapy
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C109659:bis(trihexylsiloxy) Si(IV)-tetradibenzobarreleno-octabutoxyphthalocyanine