Evaluation of photothermal effects induced
by laser heating of gold nanorods in
suspensions and inoculated tumors
G.S. Terentyuk, D.S. Chumakov, I.L. Maksimova
Saratov State University
M.V. Basko
Saratov State Medical University
A.V. Ivanov
N.N. Blokchin Russian Cancer Research Centre
B.N. Khlebtsov, N.G. Khlebtsov
IBPPM RAS, Saratov Russia
SFM'13
September 25-28, 2013, Saratov, Russia
Background
Thermal ablation of cancer is gaining increasing attention as an alternative to
standard surgical therapies , especially for patients with contraindications.
Potential benefits of thermal ablation include reduced morbidity and mortality
in comparison with standard surgical resection and the ability to treat
nonsurgical patients.
There is a wide range of ablation techniques that include : cryoablation,
radiofrequency ablation, microwave ablation, ultrasound ablation and laser
ablation.
Plasmonic photothermal therapy (PPTT) is a technique
of cancer thermal therapy based on the laser heating
of gold nanoparticles. One of the main advantages of this
therapeutic technology is its high spatial selectivity
that prevents surrounding healthy tissues
from thermal damage.
Manthe R.L. et al . Mol . Pharm (2010)
Advantages of gold nanoparticles
as antitumor photothermal agents:
1) Unique optical properties
2) Photostability
3) Low toxicity
4) Well-known synthesis protocols
Dickerson et al. Chem. Soc Rev (2011)
Goal of the research
To study photothermal effects under laser
irradiation of aqueous suspensions
of gold nanorods (in vitro experiments) and mice inoculated Erlich carcinoma after intravenous
injections of gold nanorods (in vivo experiments)
Characteristics of nanoparticles
Gold nanorods (GNR) were synthesized
by a seed-mediated approach and
functionalized with PEG
Geometrical parameters :
L = 41 ± 8 nm
d= 10,2 ± 2 nm
r = 4,03 ± 0,7
Plasmon resonance at the wavelength
820 nm
Transmission electron microscopic image
of gold nanorods
Scheme of in vitro experiments
Suspension volume – 1,5 ml
Duration of irraditaion– 5 min
Power density - 1 W/сm2
Wavelength- 810 nm
IRYSYS thermal imager was placed at
the distance 37 cm of the test tube
Dependence of the temperature increment ∆T on the concentration of gold
nanorods in the suspension after irradiation with laser light (810 nm, 1
W/сm2 ) during 5 min.
Distribution of temperature T along the axis x of test tubes under the laser
heating of gold nanorod suspensions with concentrations 8 (а) and 100 (b)
mg/ml.
(А)
(B)
Laboratory animals and tumour model
Laboratory animals
Female linear mice BALB/с
Age : 3 months
Body mass : 20-22 g
Tumour model :
Ehrlich’s ascites carcinoma
The mean volume of the tumour
was
1,7 ± 0,3 см2
Scheme of in vivo experiments
Experimental
group № 2
14 animals
Experimental
group № 1
14 animals
Laser irradiation
Wavelength - 810 nm
Duration - 5 min
Power Density- 1 W/cm2
7 animals
(ААS)
Evaluation of tumor growth
dynamic (7 animals)
Scheme of in vivo experiments
Control group
№1
6 animals
Control group
№2
6 animals
Laser irradiation
No irradiation
Wavelength - 810 nm
Duration - 5 min
Power Density- 1 W/cm2
2 animals
(AAS)
Evaluation of tumor growth
dynamic (4 animals)
2 animals
(AAS)
Evaluation of tumor growth
dynamic (4 animals)
2 D distribution of temperature over the surface of mice skin before the laser
irradiation, in 1 min and in 5 min.
before laser irradiation
1 min
5 min
Kinetics of laser heating of tumor (1) and healthy (2) tissue in the vicinity of it
maximum in 24 houres after intravenous injection of gold nanorods in the dose 2
(а) and 8 (b) mg /kg. Curve 3 shows the kinetics of the maximal heating of healthy
muscle tissue without injecting the nanoparticles.
Biodistribution of gold nanorods in tumour and muscle (a) in liver and spleen
(b) in 24 houres after intravenous injection of nanoparticles in doses 2 (1) and
8 (2) mg/kg. Curve 3 shows the corresponding distribution when injecting
saline instead of nanoparticles.
Dependences of the tumour mean volume on the number of the days passed
after perfoming a PPTT in the experimental groups with the dose of injected
gold nanorods 8 (1) and 2 mg/kg (2) and for control groups with laser irradiation
without injecting nanoparticles (3) and without laser irradiation (4).
Conclusion
1) PEG-coated nanorods with the size 40 × 10 nm in 24 houres after systemic
injection to mice with inoculated Ehrlich carcinoma are accumulated in the tumor in
the amount 4 mkg/g. In 24 houres after injection the concentration of nanoparticles
is maximal in the spleen and liver.
2) Too high concentrations of gold nanoparticles in tumour may lead to undesirable
effect of light absorption in surface layers and extremely nonuniform heat release
3) Even in the case of significant photothermal action on the tumour tissue , its
complete resorption was not achieved and in 12 days after PPTT the growth of
tumours recommenced. These results again emphasise the necessity to use
photothermotherapy in combination with chemotherapy and radiotherapy in
order to provide high efficiency of the complex therapy.