Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk,...

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Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University Alla B. Bucharskaya, Galina N. Maslyakova, Nikita A. Navolokin, Saratov State Medical University Boris N. Khlebtsov, Nikolay G. Khlebtsov, IBPPM RAS, Saratov, Russia SFM'12 September 25-28, 2012, Saratov, Russia

Transcript of Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk,...

Page 1: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina,Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin,

Saratov State UniversityAlla B. Bucharskaya, Galina N. Maslyakova, Nikita A. Navolokin,

Saratov State Medical UniversityBoris N. Khlebtsov, Nikolay G. Khlebtsov,

IBPPM RAS, Saratov, Russia

SFM'12September 25-28, 2012, Saratov, Russia

Page 2: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

After pioneering works of early 1980s, there is a significant and growing interest in developing laser therapy methods for cancer treatment

These methods are based on mechanisms of selective damage of abnormal (target) cells in the manner that is safe for surrounding normal cells

These methods use photochemical, photomechanical, and photothermal effects of laser interactions with cells and tissues

Page 3: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

It was recently established that laser-induced local heating of cellular structures (through photothermal (PT) mechanisms), using either pulsed or continuous laser radiation and mediated by light-absorbing nanoparticles and microparticles, may provide precisely localized damage that can be limited to single cells

Accumulation of light-absorbing nanoparticles in relatively transparent cells may enhance their optical absorption up to several orders of magnitude

Thus, nanoparticles (NP) act as localized sources of laser-induced heat that can cause cell damage

Even greater potential for selective damage of target (e.g., cancer) cells exists through integration of NPs allow specific targeting of the cells

PT effects of continuous wave radiation (such as hyperthermia) are most effectively used in damaging relatively large areas of abnormal tissues

However, despite apparent advantages of the laser nano-thermolysis, the full potential of this method has not been realized yet

Page 4: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Nanocomposite:Gold nanorods coated with silicon

dioxide layer with hematoporphyrine molecules (Au-SiO2-Hp) (l=108±12 nm, d=75±6 nm)

Experimental Animals: Three white autbred rats with

transplanted liver tumor were used

One rat served as a control 1 mL of the nanocomposite was

injected 1 hr before the experiment by 0.2 mL every 1 min

The rats were anaesthetized with Zoletil 50 (Virbac, France)

Irradiation: Laser (LCS-T-12, Russia) with

irradiation wavelength 808 nm, power 2 Wt, power density 2.3 Wt/cm2

Monitoring: Thermal imager (IRI4010,

IRISYS, UK) Thermocouple K-TYPE, USA)

Histological study Histilogical specimen were

taken from the sides of the tumor after photothermolysis

Description of tumor tissue specimen was made with microscope МС 100 ХР (Micros, Austria) integrated with camera Canon РС 1107 (Canon Inc., Japan) in transmitted light mode with magnification ×200

Page 5: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

TEM-imaging of nanocomposite

Fluorescent spectra of aqueous haematoporphyrin solution (broken curve) and nanocomposite suspension (solid curve)

Page 6: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Laser (808 nm)

Thermocouple

Thermal imager

Hot bench

Rat

Tumor

Page 7: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

0 2 4 6 8 10

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Temporal dependence of the tumor temperature measured with the thermal imager

Page 8: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

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Rat 1 Rat 2 Rat 3 Rat 4 (control)

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Temporal dependence of the tumor temperature measured with the thermocouple

Page 9: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Liver cancer composed of lobules of various sizes which separated by thin layers of connective tissue. Tumor cells were oval-round and had eccentrically located nucleus. A significant part of the cytoplasm was occupied by large vacuoles containing mucus

Page 10: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Necrosis are in 30-50% of tumor area

Page 11: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Tumor cells with degenerative changes are preserved only in the subcapsular zone, necrosis are almost total (90-95% of tumor area)

Page 12: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

It is shown that under action of laser irradiation (808 nm) temperature of skin surface measured with the thermal imager increases from 34.2±1.5°C up to 58.1±0.23°C for rats with the tumors sensitized by the nanocomposite and up to 48.8°C for the control rat

Temperature in the depth of the tumors measured with the thermocouple increases from 31.5±2.1°C up to 43.5±2.1°C for the all rats. It can be explained by inaccuracy of thermocouple connection

Page 13: Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University.

Grant #224014 Network of Excellence for Biophotonics (PHOTONICS4LIFE) of the Seventh Framework Programme of Commission of the European Communities

Grants # 11-02-00560 and 12-02-92610-KO of Russian Foundation of Basis Research

Russian Federation governmental contacts

02.740.11.0770, 02.740.11.0879, 11.519.11.2035, and 14.B37.21.0728