UPTAKE AND PHOTOTOXICITY OF TRICARBOCYANINE INDOLENINE DYE COVALENTLY BOUND WITH GLUCOSE (TICS) UNDER ACIDIFICATION OF TUMOR CELLS ENVIRONMENT

Istomin Yury P., Alexandrova Elena N., Chalov Vadim N., Zhavrid Edward A., Voropay Evgueny S., Samtsov Michael P., Lugovsky Anatoly P., Lugovsky Alexander А., Mikhalovsky Iosif S.

Aim: 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.
Conclusion: pH reduction of tumor cells environment improves efficacy of photodynamic treatment with TICS.