UPTAKE AND PHOTOTOXICITY OF TRICARBOCYANINE INDOLENINE DYE COVALENTLY BOUND WITH GLUCOSE (TICS) UNDER ACIDIFICATION OF TUMOR CELLS ENVIRONMENT
Yury P. Istomin1, Elena N. Alexandrova1, Vadim N. Chalov1,
Edward A. Zhavrid1, Evgueny S. Voropay2, Michael P. Samtsov2,
Anatoly P. Lugovsky2, Alexander À. Lugovsky2, Iosif S. Mikhalovsky2
1N.N. Alexandrov Research Institute of Oncology and Medical Radiology,
Ministry of Health, Minsk 223040, Belarus 2A.N. Sevchenko Research Institute of Applied Physical Problems
of Byelorussian State University, Minsk 220064, Belarus
Abstract. 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.
Key Words:cyanine dyes, HeLa cells, rat fibrosarcoma SM-1, photodynamic therapy, pH, glucose.