The assessment of lipid peroxidation in tumor-bearing rats after plasmonic photothermal treatment

WORKING GROUP Alla B. Bucharskaya, Saratov State Medical University , Russia Galina A. Afanasyeva, Saratov State Medical University, Russia Alexey V. Ivlichev, Saratov State Medical University, Russia Dmitry A. Mudrak, Saratov State Medical University, Russia Nikita A. Navolokin, Saratov State Medical University, Russia Georgy S. Terentyuk, Saratov State Medical University, Saratov State University, Russia Galina N. Maslyakova, Saratov State Medical University, Russia Boris N. Khlebtsov, Institute of Biochemistry and Physiology of Plants and Microorganisms RAS, Russia Nikolai G. Khlebtsov, Institute of Biochemistry and Physiology of Plants and Microorganisms RAS, Saratov State University, Russia Alexey N. Bashkatov, National Research Saratov State University, Russia Elina A. Genina, National Research Saratov State University, Russia Valery V. Tuchin, National Research Saratov State University, Russia

The aim of study The aim of study was to assess the the impact of plasmonic photothermal treatment (PPTT) after a single and multiple intravenous injection of polyethylene glycol (PEG) -coated gold nanorods (GNRs) on indicators of peroxidation in the serum of rats with transplanted liver cancer PC-1. TEM images of gold nanorods

Materials and methods The experiments were performed at Centre of Collective Use of Saratov State Medical University on outbred albino male rats weighing 180-220 g. GNRs: 41±8 nm (length) and 10±2 nm (diameter), concentration of 400 μg/ml - were synthesized in a laboratory of nanobiotechnologies (IBPPM RAS). 24 h after last i.v. injection of GNRs-suspension, the tumors were irradiated by the NIR 808-nm diode laser LS-2-N-808-10000 (Laser Systems, Ltd., Russia) during 15 min at power density 2.3 W/cm2. The lipid peroxidation indicators: malondialdehyde (MDA), lipid hydroperoxide (LHP), the average molecular mass (MSM) were evaluated by standart spectrophotometric methods in blood serum of rats.

Design of experiment The model of liver cancer (cholangiocarcinoma line PC-1) was reproduced by transplantation of 25% cell suspension, obtained from the bank of tumor strains of Russian Cancer Research Center n.a. N.N. Blokhin. When the tumor reached a diameter of 3.0 ± 0.3 cm3 the rats were divided into 4 groups (6 animals in group) : group 1 – without treatment, group 2 - with a single injection of 1 mL of GNR-suspension, group 3 - with double injections of 1 mL of GNR-suspension, group 4 - with triple injections of 1 mL of GNR-suspension. The half of animals from 2,3,4, groups 24 h after last i.v. injection was withdrawn from the experiment, remaining animals were treated by PPTT and were withdrawn from the experiment 24 after PPTT.

Results The indicators of lipid peroxidation: MDA(pmol/l), GPL (U/ml), AWM (U/ml) in blood serum

Results The significant increase in the level of lipid hydroperoxides (LHP) was found in blood serum of rats with transplanted liver cancer PC-1 after single and repeated intravenous injection of GNRs. Further increase of lipid hydroperoxides (LHP) was revealed 24 h after PPTT with single and repeated intravenous injection of GNRs. It noted along with increased levels of MDA and indicates the activation of lipid peroxidation as a result of PPTT exposure on tumor cells.

CONCLUSION The significant differences in levels of malondialdehyde (MDA) and lipid hydroperoxides (LHP) were revealed in blood serum of rats with transplanted liver cancer after single and repeated intravenous injection of GNRs and PPT therapy. The activation of lipid peroxidation confirms the efficiency of PPTT treatment of transplanted tumors in animals and allows to recommend the use of PEGylated gold nanorods as nanosensitizers in plasmonic photothermal treatment of tumors.

Acknowledgements This study was supported by state task of Russian Ministry of Health and partially supported by grants No. 14-13-01167 and 14-15-00186 of the Russian Scientific Foundation .