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P hotothermal and photodynamic effects at laser heating with gold nanoparticles and nanocomposits Au-SiO 2 -Hp.

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Photothermalandphotodynamiceffects at laser heating with gold nanoparticles and nanocomposits Au-SiO2-Hp

Georgy S. Terentyuk1,3, Alla B. Bucharskaya1, Andrey V. Ivanov2, Elina A. Genina3, Alexey N. Bashkatov3, Irina L. Maksimova3, Valery V. Tuchin3, Boris N. Khlebtsov4, Nikolay G. Khlebtsov4

1Saratov State Medical University n. a. V.I. Razumovsky, Saratov

2Russian Cancer Research Center n. a. N.N. Blokhin , RAMS, Moscow

3Saratov State University n. a. N.G. Chernyshevsky, Saratov

4Institute of Biochemistry, Physiology of Plants, Microorganisms RAS, Saratov

Saratov Fall Meeting 2012


Determination of gold by atomic absorption spectroscopy

gold accumulation in organs

control

15 nm

50 nm

160 nm

24 hrs after

intravenous injection

Au, μg/mL

Atomic -adsorbtion Spectrometr AAS-3 (С. Zeiss) with lamp LT-6М

Ashing с H2SO4 t=630оС

Resonance line 242,8 nm

Detection limit 0,02 μg/ml

Range of the linear region 0,2-20,0 μg/ml

blood

brain

kidneys

lungs

liver

spleen

Terentyuk et al. 2009, No. 5, 292-302


Dynamics of gold concentrations in tumor tissue intertwined after intravenous injection of gold nanoparticles

Dynamics of gold concentration in blood after intravenous injection of gold nanoparticles

Au, μg/mL

t, min

t, hrs

○- control, ●- tumor,

 - skin and muscle tissue


The value of tumor after intravenous injection of gold nanoparticlesvascularization for the passive delivery of nanoparticles


Size-dependent changes in the organs 24 hours after intravenous injection of gold nanoparticles

brain

blood separation


Setting resonances intravenous injection of gold nanoparticles

Transparency window of biological tissues

Vis

UV

NIR

Extinction

Epidermis

Dermis

Hypodermis

Wavelength, nm

Gold nanoparticles synthesized in the laboratory of biosensors and nanoscale structures of IBPPM RAS, Saratov, Russia


Comparative dynamics of heating of gold nanoparticles solutions

Temperature, oC

0.5 Wt/cm2

0.25 Wt/cm2

0.5 Wt/cm2

Time, min


The concentration of gold per gram of tissue a day after the intravenous administration

Au, μg/g

Au, μg/g

control

control

tumor

muscle

control

control

liver

spleen

С – nanocages, R - nanorods


Laser intravenous administrationthermolysisoftransplanted Ehrlich tumor in mice

Intravenous 400 μg/mL

intratumoral

intravenous

720 μg/mL

intravenous

Intravenous 50 μg/mL

90 μg/mL

T, °C

T, °C

control

control

Time of heating, min

Time of heating, min


The maximum temperature on the surface after laser heating intravenous administration

a

b

The kinetics of laser heating of the tumor (1) and health (2) tissues in its maximum one day after intravenous injection of gold nanorods at 2 (a) and 8 mg / kg (b). Curves 3 is the kinetics of maximum heating of healthy tissue without introducing nanoparticles (control)


The temperature distribution on the surface of the animal's skin with intravenous injection of nanoparticle - surface laser heating of the tumor

T, °C

0 - before heating; 1-5 after 1-5 minutes after the start of heating, respectively; 6-8 after 1-3 minutes after the heating, respectively


Control - heating without nanoparticles, in a day skin with intravenous injection of

Experiment - heating with nanoparticles in a day


Transplanted Ehrlich tumor -external irradiation skin with intravenous injection of

experiment

control

1 min

5 min

0 min


Interstitial hyperthermia with skin with intravenous injection of nanorods using a catheter with a fiber diffuser

Р=1.5 Vtt=15 minL=10 mm


Pathology of tumor tissues after skin with intravenous injection of controlled laser thermolysis using plasmon-resonant gold nanoparticles

Tissue of transplanted rat kidney cancer before exposure

hematoxylin-eosin stain

Increase Х150

Without nanoparticles

With gold nanoparticles

Tumor tissue after laser exposure


Growth dynamics of subcutaneously transplanted kidney cancer in rats before and after laser hyperthermia, CW, 1 Watt, 30 min

Laser

action

Tumor size, cm3

thermogram of tumor without nanoparticles

A day after tumor transplantation

○ - control, ■ - laser heating without nanoparticles

▲ - laser heating after intravenous injection of nanoparticles, 1 ml

 - laser heating after interstitial injection of nanoparticles, 0.2 mL

thermogram of tumor interstitial introduction of nanoparticles to a depth of 7 mm


Dependence of the mean tumor volume on the number of days in rats before and after laser hyperthermia, CW, 1 Watt, 30 min

passed after PPTT

Tumor volume, cm3

Number of days

experimental groups with doses of administered gold nanorods: 8 (1) and 2 mg / kg (2), control groups under laser irradiation without introducing nanoparticles (3) and without laser irradiation (4)


Nanocomposites in rats before and after laser hyperthermia, CW, 1 Watt, 30 min: vitrified gold-silver nanocages modified Yb-HP


Au-NR in rats before and after laser hyperthermia, CW, 1 Watt, 30 min-SiO2-HP

IR-laser ~2.3 Wt/cm2 He-Ne laser ~160 mWt/сm2

Tumor (20 min of exposure)

Tumor before exposure

(V= 3 сm3)

Tumor after 72 hours

(V= 0.16 сm3)


Three variants of the protocol for Au-NR in rats before and after laser hyperthermia, CW, 1 Watt, 30 min-SiO2-HP

PTD→12 hours→LTT

a) absence of optical postthermal obstacles

b)exclusion of thermal effects

c) hemostasis (2-12 hours): it is benefit for thermotherapy as heat loss reduces

d) decrease in the partial pressure of oxygen and pH increases thermal sensitivity

e) LTT inhibits repair of necrotic cells

  • PTD + LTT

  • LTT accelerates chemical reactions

  • Synergistic effects on blood vessels (stasis, collapse)

  • Synchronicity subsequent processes in the tumor tissue

LTT→24 hours→PDT

a) direct necrosis

b) hemostasis - partial reduction of oxygen and pH

c) 24 hours restore of blood flow

d) 24 hours - pic HSP70

e) resumption of protein synthesis 12-26 hours

f) PDT inhibits repair of cells

1) the size of tumors < 3 cm3

2) Temperature 50-75 °C - to avoid the formation of coagulation optical barrier


Thank you! in rats before and after laser hyperthermia, CW, 1 Watt, 30 min


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