Photocytotoxic efficacy of sulphonated species of aluminium phthalocyanine against cell monolayers, multicellular spheroids and in vivo tumours.
The problem of relying solely on in vitro data to predict photosensitiser efficacy was demonstrated by examining the uptake and the ability to mediate photocytotoxicity of mono-, di-, tri- and tetra-sulphonated species of chloroaluminium phthalocyanine (AlS1-4Pc) in monolayer cultures of murine Colo 26 cells and in both monolayer and spheroid cultures of human WiDr cells. Cells treated in vitro, whether in monolayer or as spheroids, with the less sulphonated derivatives, AlS1Pc and AlS2Pc, were more susceptible to photocytotoxicity than those treated with AlS3Pc, cells treated with AlS4Pc were even less susceptibile to the cytotoxic effects of light irradiation. Generally these results mirrored the cellular uptake in vitro. When WiDr spheroids were increased in size from 250 microns to 500 microns there was a reduction in uptake of AlS1Pc and AlS2Pc which was reflected by the decreased sensitivity of the larger spheroids to the effects of light irradiation. AlS1Pc had no effect against Colo 26 cells growing as s.c. tumours in syngeneic BALB/c mice; whereas AlS3Pc, AlS2Pc and AlS4Pc produced significant reductions in tumour weights 5 days post laser light irradiation. Of these, AlS2Pc had the most dramatic effect on the colony forming efficiency of tumour cells recovered 24 h after PDT. While, despite their effects on tumour size, AlS3Pc and AlS4Pc scarcely affected the subsequent viability of cells from dissociated tumours. Thus the in vitro efficacy of the sulphonated species of phthalocyanines is not necessarily predictive of their in vivo effectiveness.
Chan
W S
WS
Biology of Metastasis Laboratory, Imperial Cancer Research Fund, London, UK.
West
C M
CM
Moore
J V
JV
Hart
I R
IR
D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C063071:aluminum(III) phthalocyanine trisulfonic acid