Uptake and phototoxicity of tricarbocyanine indolenine dye covalently bound with glucose (TICS) under acidification of tumor cells environment.
OBJECTIVE
To evaluate the influence of pH on accumulation and photocytotoxicity of the novel tricarbocyanine indolenine dye covalently bound with glucose (TICS).


METHODS
For in vitro experiments, cultured HeLa cells were incubated with TICS at pH 7.1, 6.5 or 6.2 and then scored for dye uptake, viability and sensitivity to laser (740 nm) irradiation. In vivo TICS was injected to rats with implanted subcutaneously SM-1 tumor and then dye accumulation and tumor necrosis depth after laser irradiation were defined.


RESULTS
Reduction of medium pH in vitro was shown to increase in cellular TICS contents and to enhance as its "dark" cytotoxicity, and photocytotoxicity. The ratio of "dark" cytotoxicity to photocytotoxicity parameters increased 2-fold with decreasing pH value. In vivo infusion of glucose (10 g/kg) to rats resulted in improved selectivity of TICS accumulation and increase in tumor necrosis depth after laser irradiation.


CONCLUSIONS
pH reduction of tumor cells environment improves efficacy of photodynamic treatment with TICS.
Istomin
Yury P
YP
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Ministry of Health, Minsk 223040, Belarus. Istomin@users.med.by.
Alexandrova
Elena N
EN
Chalov
Vadim N
VN
Zhavrid
Edward A
EA
Voropay
Evgueny S
ES
Samtsov
Michael P
MP
Lugovsky
Anatoly P
AP
Lugovsky
Alexander A
AA
Mikhalovsky
Iosif S
IS
D000818:Animals; D001692:Biological Transport; D002232:Carbocyanines / Q000493:pharmacokinetics* / Q000528:radiation effects / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000493:pharmacokinetics / Q000528:radiation effects / Q000633:toxicity; D005947:Glucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000528:radiation effects / Q000633:toxicity; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007834:Lasers; D009368:Neoplasm Transplantation; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000528:radiation effects / Q000633:toxicity; D051381:Rats
D002232:Carbocyanines; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D005947:Glucose