Evaluation of photothermal effects induced by laser heating of gold nanorods in suspensions and inoculated tumors - PowerPoint PPT Presentation

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Evaluation of photothermal effects induced by laser heating of gold nanorods in suspensions and inoculated tumors

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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 – PowerPoint PPT presentation

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Title: Evaluation of photothermal effects induced by laser heating of gold nanorods in suspensions and inoculated tumors


1

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
2
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.

3
  • 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.
  • Advantages of gold nanoparticles
  • as antitumor photothermal agents
  • Unique optical properties
  • Photostability
  • Low toxicity

Manthe R.L. et al . Mol . Pharm (2010)
Dickerson et al. Chem. Soc Rev (2011)
4
  • 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)

5
 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
6
Scheme of in vitro experiments
  • Suspension volume 1,5 ml
  • Duration of irraditaion 5 min
  • Power density - 1 W/?m2
  • Wavelength- 810 nm
  • IRYSYS thermal imager was placed at the distance
    37 cm of the test tube

7
  • Dependence of the temperature increment ?T on
    the concentration of gold nanorods in the
    suspension after irradiation with laser light
    (810 nm, 1 W/?m2 ) during 5 min.

8
Distribution of temperature T along the axis x
of test tubes under the laser heating of gold
nanorod suspensions with concentrations 8 (?)
and 100 (b) mg/ml.
(B)
(?)
9
Laboratory animals and tumour model
  • Laboratory animals
  • Female linear mice BALB/?
  • Age 3 months
  • Body mass 20-22 g
  • Tumour model
  • Ehrlichs ascites carcinoma
  • The mean volume of the tumour was
  • 1,7 0,3 ??2

10
Scheme of in vivo experiments
Experimental group ? 2
Experimental group ? 1
14 animals
14 animals
Laser irradiation Wavelength - 810 nm Duration -
5 min Power Density- 1 W/cm2
  • Evaluation of tumor growth dynamic (7 animals)
  • 7 animals
  • (??S)

11
Scheme of in vivo experiments
Control group ? 1
Control group ? 2
  • 6 animals

6 animals
Laser irradiation Wavelength - 810 nm Duration -
5 min Power Density- 1 W/cm2
No irradiation
Evaluation of tumor growth dynamic (4 animals)
Evaluation of tumor growth dynamic (4 animals)
2 animals (AAS)
2 animals (AAS)
12
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

13
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 (?) and 8 (b) mg
/kg. Curve 3 shows the kinetics of the maximal
heating of healthy muscle tissue without
injecting the nanoparticles.
14
  • 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.

15
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).
16
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.
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