Photothermal and photodynamic
effects 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
control
15 nm
50 nm
160 nm
gold accumulation in organs
blood
liver
lungs
spleen
Resonance line
242,8 nm
kidneys
Ashing с H2SO4
t=630оС
brain
Atomic -adsorbtion
Spectrometr AAS-3
(С. Zeiss) with lamp
LT-6М
Au, μg/mL
24 hrs after
intravenous injection
Detection limit
0,02 μg/ml
Range of the linear
region 0,2-20,0
μg/ml
Terentyuk et al. 2009, No.
2
5, 292-302
Dynamics of gold concentrations
in tumor tissue intertwined after
intravenous injection of gold
nanoparticles
Au, μg/mL
Dynamics of gold
concentration in blood after
intravenous injection of gold
nanoparticles
t, min
t, hrs
○- control, ●- tumor,
 - skin and muscle tissue
3
The value of tumor vascularization for the passive delivery of nanoparticles
Size-dependent changes in the organs 24 hours after intravenous
injection of gold nanoparticles
kidneys
plethora
degeneration of
tubular epithelium
violation of the
vascular wall
pigment in the lumen
of blood vessels
damage to the
glomeruli
liver
brain
violation of the
structure
plethora of sinusoids
pigment in Kupfer
cells
pigment in
parenchyma
blood separation
dystrophy of
hepatocytes
spleen
violation of the
structure
plethora
pigment in folliculs
pigment in red pulpa
apoptosis
Violation of artery
wall
blood separation
15 nm
++
++
50 nm
++
+
160 nm
+
+
+
-
+
+
+
_
_
++
+
15 nm
-
50 nm
-
160 nm
-
+
+
+
+
+
+
+
_
+
+++
+
+
-
15 nm
-
50 nm
++
160 nm
_
++
+
+++
-
+++
++
++
++
-
+
+
+
+
5
Setting resonances
Transparency window of
biological tissues
Extinction
UV
Vis
NIR
Epidermis
Dermis
Hypodermis
Wavelength, nm
Gold nanoparticles
synthesized in the laboratory
of biosensors and nanoscale
structures of IBPPM RAS,
Saratov, Russia
6
Comparative dynamics of heating of gold nanoparticles solutions
0.5 Wt/cm2
Temperature, oC
0.25 Wt/cm2
0.5 Wt/cm2
Time, min
Au, μg/g
Au, μg/g
The concentration of gold per gram of tissue a day after the
intravenous administration
control
tumor
control
control
muscle
liver
С – nanocages, R - nanorods
control
spleen
Laser thermolysis of transplanted Ehrlich tumor in mice
intratumoral
Intravenous 400 μg/mL
intravenous
720 μg/mL
intravenous
Intravenous 50 μg/mL
control
Time of heating, min
T, °C
T, °C
90 μg/mL
control
Time of heating, min
The maximum temperature on the surface after laser heating
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)
T, °C
The temperature distribution on the surface of the animal's skin with
intravenous injection of nanoparticle - surface laser heating of the
tumor
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
Experiment - heating with
nanoparticles in a day
Transplanted Ehrlich tumor -external
irradiation
experiment
0 min
control
1 min
5 min
Interstitial hyperthermia with nanorods using a catheter with a fiber diffuser
Р=1.5 Vt
t=15 min
L=10 mm
Pathology of tumor tissues after 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
15
Growth dynamics of subcutaneously transplanted kidney cancer in
rats before and after laser hyperthermia, CW, 1 Watt, 30 min
Tumor size, cm3
Laser
action
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
16
depth of 7 mm
Tumor volume, cm3
Dependence of the mean tumor volume on the number of days
passed after PPTT
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: vitrified gold-silver nanocages modified Yb-HP
Au-NR-SiO2-HP
IR-laser ~2.3 Wt/cm2
Tumor before
exposure
(V= 3 сm3)
He-Ne laser ~160 mWt/сm2
Tumor (20 min of
exposure)
Tumor after 72
hours
(V= 0.16 сm3)
Three variants of the protocol for Au-NR-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
a) LTT accelerates chemical
reactions
b) Synergistic effects on
blood vessels (stasis,
collapse)
c) 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!