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Energy-based Treatment of Tissue and Assessment VI



Modelling and characterization of photothermal
effects assisted with gold nanorods in ex-vivo
        samples and in a murine model
                        AUTHORS:
     Félix Rodríguez Jara1, Horacio Lamela Rivera2 and
                   Vincent Cunningham3
                        1felix.rjara@alumnos.uc3m.es

                           2horacio@ing.uc3m.es

                             3vcunning.uc3m.es




    OPTOELECTRONICS AND LASER TECHNOLOGY GROUP
        ELECTRONIC TECHNOLOGY DEPARTMENT
                  San Francisco (CA), January 23th, 2011
0. General Index.
1. Introduction
                          General Index:
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.
                          1. Introduction
2. Opto-thermal
   modelling for
   photo-thermal          2. Opto-thermal modelling for Photo-Thermal Therapy
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.
                          3. Experimental Results
3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
                          4. Conclusions and Future Work
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                            Modelling and characterization of photothermal effects assisted with
  1                                              gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          General Index:
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
                                    1. Introduction
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                      Modelling and characterization of photothermal effects assisted with
  2                                        gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          1.1 The Motivation.
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.      CANCER, one of the main causes of mortality all around the world.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
                                   - 7.4 Millions out of the total deaths per year ≈ 13 % (WHO)
 1.5 The Design.


2. Opto-thermal
   modelling for          Need of investigation in new therapy techniques
   photo-thermal
   therapy.                                Mortality and side effects
  2.1 Approach
  2.2 Finite Element
      Modelling.
                                           Number of patients that can be trated
3. Experimental
   Results.                                Laser hyperthermia technique
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo   Collaboration with a specialized Company in
4. Conclusions and        Animal models
   Future Work
                                   - Good Laboratory Practices (GLP)
                                   - Qualified Staff
                                   - Ethical Committee
                                                Modelling and characterization of photothermal effects assisted with
  3                                                  gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          1.2 The hyperthermia technique: the GOAL
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
                          Hyperthermia temperature                                       Tumoral Cell death
     therapy.                (from 42ºC to 65 ºC)
 1.5 The Design.
                          held during various minutes
2. Opto-thermal                                                                          GOAL: 80% Tumour
                                    (3-10’)
   modelling for
   photo-thermal
                                                                                         tissue ablation
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.                                       42 ºC – 65 ºC
3. Experimental
   Results.                                               Tumour
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
                                           37 ºC
      Results – in-vivo
                                                           5-10 mm
4. Conclusions and
   Future Work
                                                                                 Biological Tissue


                                           Hyperthermia temperature selected:
                                                         55 ºC
                                          ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA
  4                                       CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
0. General Index.
                          1.2 The Hyperthermia Technique: State-of-
1. Introduction
 1.1 The Motivation       The-Art
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.                                                               Registro Tª
 1.5 The Design.                                                                                       Láseres alta potencia
                                                                                                   estado sólido (Nd:YAG, OPO)
2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach             Radiofrecuencia
  2.2 Finite Element
      Modelling.          Ultrasonidos (HIFU)
3. Experimental
                                                                                                    Fibra óptica + Difusor
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
                                                                     Tumor
      Results – in-vivo


4. Conclusions and                                                                                   Tejido biológico
   Future Work


                                         - Low selectivity
                                         - Use high amounts of energy
                                         - Very expensive devices with big dimensions
                                                Modelling and characterization of photothermal effects assisted with
  5                                                  gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          1.3 The Photo-thermal Therapy System
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology                            HIGH
     in Photo-thermal                         POWER
     therapy.                                 LASER
 1.5 The Design.
                                              DIODE
2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element         Temperature
      Modelling.               Register


3. Experimental                        Superficial
   Results.
                                                         λ= 808
  3.1 Experimental Set-
                                                           nm
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo
                                                                                                           Nanoparticle
                                Interna                                                                      infusion:
4. Conclusions and                                                                                       Intratumoural or
   Future Work                                                                                            Intravenous ?
                                                     Biological
                                                      Tissue




                                                     Modelling and characterization of photothermal effects assisted with
  6                                                       gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          1.4 Nanotechnology in Photo-Thermal Therapy
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
                             Gold Nanoparticles
                             GOLD NANORODS
     in Photo-thermal
     therapy.
 1.5 The Design.               Tuned optical
                                                                                        EFFICIENCY                                                                                POWER
2. Opto-thermal                 absorbance
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo   Fig. adapted of “Cancer Research”, 69(9):1-9, (2009)
  3.3 Experimental
      Results – in-vivo                                                                                        1.5




                            - Passive                                                                                                                           A                 A Longitudinal
4. Conclusions and
                                                                                                                                                                                  Surface Plasmon
   Future Work
                            - Harmless
                                                                                                                1
                                                                                           Absorción [cm -1]



                                                                                                                                                                                  Resonance Peak

                                                                                                                      B                                                           B Axial
                                                                                                               0.5

                                                                                                                                                                                  Surface Plasmon
                                                                                                                                                                                  Resonance Peak

                                                                                                                0
                                                                                                                400   500   600      700         800      900       1000   1100

                                                                                                                                  Longitud de onda [nm]



                                                                 Modelling and characterization of photothermal effects assisted with
  7                                                                   gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          1.5 The Design: Experimental studies
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.                   Efficiency Study                                                         Efficacy Study
  2.1 Approach
  2.2 Finite Element
      Modelling.
                                                                                                   CT-26 COLON CANCER
                              OPTIMIZE THE SET-UP
3. Experimental                                                                                    XENOGRAFT STUDIES
   Results.
  3.1 Experimental Set-   - Number of animales for group -> Statistics                         - Tumour size?
      up.
  3.2 Experimental
      Results – ex-vivo
                          - System design in terms of efficiency:                              - Stops Tumor growing?
  3.3 Experimental
      Results – in-vivo   (Power, Irradiance, Nanoparticle Concentration)                      - Ablation of the tumoral tissue?
4. Conclusions and        - Therapy parameters
   Future Work
                          (Exposure time, way of application)
                          - Ethical Committee (international directives of
                          animal handling) -> HEATING UP, NOT BURNING
                          OR CHARRRING

                                                 ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA
  8                                              CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
0. General Index.
1. Introduction
                          General Index:
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
                          2. Opto-thermal Modelling for
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
                              Photo-Thermal Therapy
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                    ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA
  10                                CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
0. General Index.
1. Introduction
                          2.1 Approach
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
                                                                                    Energy
                          Optical power,                                                                                               Temperature
 1.5 The Design.                                                                   Deposition                 Transferencia
                             Irradiance             Fuentes térmicas
                                                                                                                 térmica
2. Opto-thermal           P [W], I [W/cm2]
   modelling for
   photo-thermal
   therapy.                                         Optical properties                             Physical and thermal properties
  2.1 Approach                                         of the tissue                                         of the tissue
  2.2 Finite Element
      Modelling.
                                                    µa [cm-1], µs [cm-1]                           ρ[kg/m ]C [JKg-1K-1, k [Wm-1K-1],
                                                                                                         3



3. Experimental
   Results.                                            Thermal Source
  3.1 Experimental Set-
      up.
  3.2 Experimental                  Optical Power
      Results – ex-vivo
  3.3 Experimental                                                                                                              Thermal Energy
      Results – in-vivo                                                                                                           Transferred
                                                                                                                    Temp

4. Conclusions and
   Future Work                                                  dV                                                       dV

                                               Tissue absorption + Nanoparticles

                                       µtotal = µtissue+µnanoparticles

                                                         Modelling and characterization of photothermal effects assisted with
  11                                                          gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          2.2 Finite Element Modelling (FEM)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.      - Less computational resources needed
 1.4 Nanotechnology
     in Photo-thermal
                          - It can be applied to complex geometries
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for                                                     Energetic
                                    Initial                                                                   Thermal
   photo-thermal                                                   Contribution.
                                 Temperature                                                                  Energy
   therapy.                                                        Laser energy
                                    37 ºC                                                                  transference
  2.1 Approach                                                      absorption
  2.2 Finite Element
      Modelling.


3. Experimental
                                                                                NO
   Results.
  3.1 Experimental Set-                                             Stop time                              Temperatures
      up.
  3.2 Experimental                                                  reached?                                  update
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo
                                                                                YES
4. Conclusions and
   Future Work

                                                                      Final
                                                                   Temperature




                                               Modelling and characterization of photothermal effects assisted with
  14                                                gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          General Index:
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
                               3. Experimental Results
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




  15
0. General Index.
1. Introduction
                          3.1 Experimental Set-up (I)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
                          Optoelectronic General Schema
 1.4 Nanotechnology                                                                            Thermocouple
     in Photo-thermal
     therapy.
                                                                                                thermometer
 1.5 The Design.

                                                                                                                        Sonda termopar
2. Opto-thermal
                                                                                  Lentes de                               hipodérmica
   modelling for
   photo-thermal                     Cabezal láser                                 acoplo                               (HYP-1, Omega)
                                                         Soporte
   therapy.                    (CNI-MDL-H-808-5000, CNI)                                                 d1
  2.1 Approach
  2.2 Finite Element                                                                                                   Diámetro del haz
      Modelling.
                                                                                                                          (FWHM)
                                                                               d0
3. Experimental                                 Fibra óptica




                                                                                                             d2
   Results.                                                        l1                        l2
  3.1 Experimental Set-
                                          (CNI-SMA-Fibre-600, CNI)
      up.
  3.2 Experimental
      Results – ex-vivo
                                                               l1 = l2                                              Tejido irradiado
  3.3 Experimental                                        f1= f2 = 2.54 cm
      Results – in-vivo                                  D1 = D2= 2.54 cm
                                                                                          Termómetro infrarrojo
4. Conclusions and
                                                                                          (OS-530LE, Omega)
   Future Work




                                   Driver
                              (PSU-H-LED, CNI)

                                             Modelling and characterization of photothermal effects assisted with
  16                                              gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.1 Experimental Set-up (II)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
                          Experimental Set-up for therapy application in ex-vivo tissue samples
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                              Modelling and characterization of photothermal effects assisted with
  17                                               gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.1 Experimental Set-up (and III)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
                          Experimental set-up for therapy application in mice (in-vivo)
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                               Modelling and characterization of photothermal effects assisted with
  18                                                gold nanorods in ex-vivo samples and in a murine model
0. General Index.
                          3.1 Experimental Set-up:
1. Introduction
 1.1 The Motivation       Development Stages
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
                          Develpment Stages of the Photo-Thermal Therapy System
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.                  Requirements
 1.5 The Design.                and Goals                        Optimization loop
                                                                                                    Optimization
                                                                                                       of the
2. Opto-thermal
                                                                                                      System
   modelling for
   photo-thermal
   therapy.
  2.1 Approach                      Concept, Design                Biological Model
  2.2 Finite Element                                                                                       Experimental
                                   and Implementation                   ex-vivo
      Modelling.
                                      of the system                  (tissue samples)                        Results
3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
                                                                      Experimental                       Biological Model
  3.3 Experimental                                                                                            in-vivo
      Results – in-vivo                                                 Results                                 (ratones)

4. Conclusions and
   Future Work

                                                                                                  Optimization
                                       Clinical
                                                                                                     of the
                                      Application                                                   System
                                    (Human Beings)


                                                 Modelling and characterization of photothermal effects assisted with
  19                                                  gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.2 Experimental results - ex-vivo (I)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
                          Sample preparation:
 1.4 Nanotechnology
     in Photo-thermal     - Fresh chicken muscle tissue.
     therapy.
 1.5 The Design.
                          - Previous marking for infrared thermometer alineation.
2. Opto-thermal
   modelling for          - Hypodermical infusion of nanoparticles (Ntracker 30-PM-850, NANOPARTz,
   photo-thermal          saline solution PH = 7.4, 0.1 ml, OD = 25).
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




                                                Modelling and characterization of photothermal effects assisted with
  20                                                 gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                                       3.2 Experimental results - ex-vivo (II)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
                                       Looking for the optimal irradiance, experimental results.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.          55
                                                                                                                        Pbeam = 1.25 W
 1.5 The Design.                                        Phaz = 0.5 W, IFWHM = 0.95 [W/cm2], Láser+NRds
                                                           Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Láser+NRds
2. Opto-thermal
                                  50                    Phaz = 0.75 W, IFWHM = 1.43 [W/cm2], Láser+NRds
                                                                                                                         IFWHM = 2.38 W/cm2
                                                           Phaz = 0.5 W, FWHM = 0.95 [W/cm2
                                                        Phaz = 1.00 W, IFWHM =I 1.90 [W/cm2], Láser+NRds ], Solo Láser
   modelling for                                  40
                                                        Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Láser+NRds 2
                                                                                                                        ΔT = 31 ºC
                                  45
                                                           Phaz = 0.75 W, IFWHM = 1.43 [W/cm ], Solo Láser
   photo-thermal                                        Phaz = 0.5 W, IFWHM = 0.95 [W/cm2], Solo Láser
                        T [ºC]




   therapy.                       40                       Phaz = 1.00 W, IFWHM = ], Solo Láser 2
                                                        Phaz = 0.75 W, IFWHM = 1.43 [W/cm21.90 [W/cm ], Solo Láser
                                                  35
  2.1 Approach                                          Phaz = 1.00 W, IFWHM = 1.90 [W/cm22.38 [W/cm2], Solo Láser
                                                           Phaz = 1.25 W, IFWHM = ], Solo Láser
  2.2 Finite Element              35
                                                        Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Solo Láser
      Modelling.
                                                  30
                                  30
3. Experimental
   Results.                       25              25
  3.1 Experimental Set-
                                        T [ºC]




      up.               20
  3.2 Experimental                                20
                                                   50        100               150               200             250            300
      Results – ex-vivo                                                Tiempo de exposición [sg]
  3.3 Experimental
      Results – in-vivo
                                                  15

4. Conclusions and
   Future Work                                    10

                                                                                                                             ΔT = 3 ºC
                                                   5



                                                   0
                                                    0                50                      100                       150               200                250   300
                                                                                                         Tiempo de exposición [sg]
                                                                                                            Exposure Time [s]
                                                                                     Modelling and characterization of photothermal effects assisted with
  22                                                                                      gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.3 Experimental Results - in-vivo (I)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.      Animal model
 1.4 Nanotechnology
     in Photo-thermal     - Female mice, albines, BALB/c (BALB/cAnNHsd) , specific patogens free.
     therapy.
 1.5 The Design.
                          - Animals were handled by qualified staff in a company with the Good Laboratory Practice Certificate
                          (GLP)
2. Opto-thermal
   modelling for          Animal preparation
   photo-thermal
   therapy.               - Random distribution by weigth.
  2.1 Approach
                          - Identification of each animal.
  2.2 Finite Element
      Modelling.
                                                                                            Identification
                          - Hair removing from the exposed area.                               marks                                Shaving of
3. Experimental           - Light anaesthesya Ketamine/Xilacine (10μl/g).                                                        irradiated area
   Results.
  3.1 Experimental Set-   - Hypodermic infusion of nanoparticles
      up.
  3.2 Experimental         (Gold Nanorods, Ntracker).
      Results – ex-vivo
  3.3 Experimental        - Laser irradiation exposure.
      Results – in-vivo


4. Conclusions and
                                                                                                                 Positioning
   Future Work                                                                                                    platform



                                                                                                                  Laser beam
                                                                                                                   direction



  27                                                      Modelling and characterization of photothermal effects assisted with
                                                               gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.3 Experimental Results - in-vivo (II)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
                          Study of the thermal increment induced as a function of laser irradiance.
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
                                                                                        Pbeam = 1.25 W
     therapy.
 1.5 The Design.
                                     35
                                                                                         IFWHM = 2.38 W/cm2
                                           HYP: P = 0.5 W
2. Opto-thermal
   modelling for
                                           SUP: P = 0.5 W
                                           HYP: P = 1 W
                                                                                        ΔT = 29.9 ºC
                                     30
   photo-thermal                           SUP: P = 1 W
   therapy.                                HYP: P = 1.25 W
  2.1 Approach                             SUP: P = 1.25 W
                                     25
  2.2 Finite Element
      Modelling.


3. Experimental                      20
                           T [ºC]




   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
                                     15
                                                                                  12 ºC
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo              10

4. Conclusions and
   Future Work                        5



                                      0
                                       0              50                         100                         150                    200   240
                                                                              Tiempo de exposición [sg]
                                                                                 Exposure Time [s]



  28                                                         Modelling and characterization of photothermal effects assisted with
                                                                  gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                           3.3 Experimental Results - in-vivo (III)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal                        Proof of concept,                    Phaz = 1.25 W
     therapy system.
                                              experimental results.
 1.4 Nanotechnology
     in Photo-thermal
                                                                                     IFWHM = 2.38 W/cm2
     therapy.
 1.5 The Design.
                                              60                                   T = 57.8 ºC
2. Opto-thermal
   modelling for
                                              55
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
                                              50
      Modelling.
                           Temperatura [ºC]
                          Temperature [ºC]




3. Experimental                               45
   Results.
  3.1 Experimental Set-
                                                                                   T = 38.1 ºC
      up.
                                              40
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo
                                              35

4. Conclusions and                                                                                                           HYP: Gold Nanorods + Láser
   Future Work                                                                                                               SUP: Gold Nanorods + Láser
                                              30                                                                             HYP: PBS + Láser
                                                                                                                             SUP: PBS + Láser

                                              25
                                                0         100            200                    300                    400               500              600
                                                                                 Tiempo de exposición [sg]
                                                                                  Exposure time [sg]



  33                                                              Modelling and characterization of photothermal effects assisted with
                                                                       gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.3 Experimental Results - in-vivo (IV)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal    Aspect of the skin after irradiation.
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for                         Skin exposed to the laser
   photo-thermal                           Superficiebeam expuesta
                                                     de piel
   therapy.                                    a la radiación láser
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




  34                                           Modelling and characterization of photothermal effects assisted with
                                                    gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          3.3 Experimental Results - in-vivo (V)
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal    Proof of concept, FEM
     therapy system.
 1.4 Nanotechnology       Modelling.
     in Photo-thermal
     therapy.
 1.5 The Design.                        16


2. Opto-thermal                         14
   modelling for
   photo-thermal
                                        12
   therapy.
  2.1 Approach
  2.2 Finite Element
                                        10
      Modelling.
                              T [ºC]




3. Experimental                          8
                                                    The superficial thermal gradient registered
   Results.
  3.1 Experimental Set-
                                                    experimentally was of 14.75 ºC, while the
      up.
  3.2 Experimental
                                         6
                                                    modelled one was of 14.86. This is an absolute
      Results – ex-vivo
  3.3 Experimental                       4
                                                    error less than 0.11 ºC (0.75 %)
      Results – in-vivo

                                                                                                                     Superficial. Laser + NRds. EXP
4. Conclusions and                       2
                                                                                                                     Superficial. Laser + NRds. FEM
   Future Work
                                         0
                                          0   100                 200                  300                 400                  500                   600
                                                                         Exposure exposición [sg]
                                                                         Tiempo de
                                                                                   time [sg]




  35                                                 Modelling and characterization of photothermal effects assisted with
                                                          gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                          General Index:
 1.1 The Motivation
 1.2 The hyperthermia
       technique.
 1.3 The Photo-thermal
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
 1.5 The Design.


2. Opto-thermal
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
  2.2 Finite Element
      Modelling.


3. Experimental
                          4. Conclusions and future
   Results.
  3.1 Experimental Set-
      up.
  3.2 Experimental
                             work
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo


4. Conclusions and
   Future Work




  37                                  Modelling and characterization of photothermal effects assisted with
                                           gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                            4.1 Conclusions:
 1.1 Motivation
 1.2 The hyperthermia
     technique
 1.3 Photo-thermal             The laser hyperthermia therapy system using gold nanoparticles
     therapy system.
 1.4 Nanotechnology            has been demonstrated to be VIABLE in a mice model.
     in Photo-thermal
     therapy.
 1.5 Design.
                               Only the tissue injected with nanoparticles reaches hyperthermia
2. Opto-thermal                temperatures.
   modelling for
   photo-thermal
   therapy.
  2.1 Approach
                               The tissue exposed to the laser beam, but NO injected with
  2.2 Energy Balance           nanoparticles, remains unaltered (it does not reach hyperthermia
  2.3 Implemention of the
      solution. FEM.
  2.4 Finite Element
                               temperature)
      Modelling.


3. Experimental                The stablished irradiance does not induce tissue charring or skin
   Results.
  3.1 Experimental Set-
                               burning.
      up.
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
                               The computational model implemented allows to make accurate
      Results – in-vivo
                               estimations of the final temperature of the irradiated tissue with
4. Conclusions and             nanoparticles.
   Future Work




  38                                          Modelling and characterization of photothermal effects assisted with
                                                   gold nanorods in ex-vivo samples and in a murine model
0. General Index.
1. Introduction
                            4.2 Future work
 1.1 Motivation
 1.2 The hyperthermia
     technique
 1.3 Photo-thermal
                               Modelling and implementation
     therapy system.
 1.4 Nanotechnology
     in Photo-thermal
     therapy.
                               Study and design of new techniques of optical energy irradiation:
 1.5 Design.                   contact applicators, more than one laser source, pulsed light.
2. Opto-thermal
   modelling for
                               Design and test of an integrated control and monitorization
   photo-thermal
   therapy.                    system:
  2.1 Approach                                      Tissue                                   Temp.
  2.2 Energy Balance                              temperature                               register
  2.3 Implemention of the
      solution. FEM.
  2.4 Finite Element
      Modelling.

                                                                      Laser power
3. Experimental
   Results.
  3.1 Experimental Set-
      up.                      Experimental study
  3.2 Experimental
      Results – ex-vivo
  3.3 Experimental
      Results – in-vivo        Tumor model in mice to test the efficacy of the system
4. Conclusions and                 -Determine if the tumour growing is stopped and finally, the tumour is
   Future Work                     ablated.
                                   - 15 animals (BALB/c)
                                   - Cell line CT-26 mice colon cancer (CT26.WT)

  39                                           Modelling and characterization of photothermal effects assisted with
                                                    gold nanorods in ex-vivo samples and in a murine model
Thank you for your attention!




                                                                      Have a nice day.



                ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA
40              CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO

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Bios 7901 - 12

  • 1. Energy-based Treatment of Tissue and Assessment VI Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model AUTHORS: Félix Rodríguez Jara1, Horacio Lamela Rivera2 and Vincent Cunningham3 1felix.rjara@alumnos.uc3m.es 2horacio@ing.uc3m.es 3vcunning.uc3m.es OPTOELECTRONICS AND LASER TECHNOLOGY GROUP ELECTRONIC TECHNOLOGY DEPARTMENT San Francisco (CA), January 23th, 2011
  • 2. 0. General Index. 1. Introduction General Index: 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 1. Introduction 2. Opto-thermal modelling for photo-thermal 2. Opto-thermal modelling for Photo-Thermal Therapy therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental 4. Conclusions and Future Work Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work Modelling and characterization of photothermal effects assisted with 1 gold nanorods in ex-vivo samples and in a murine model
  • 3. 0. General Index. 1. Introduction General Index: 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 1. Introduction 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work Modelling and characterization of photothermal effects assisted with 2 gold nanorods in ex-vivo samples and in a murine model
  • 4. 0. General Index. 1. Introduction 1.1 The Motivation. 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. CANCER, one of the main causes of mortality all around the world. 1.4 Nanotechnology in Photo-thermal therapy. - 7.4 Millions out of the total deaths per year ≈ 13 % (WHO) 1.5 The Design. 2. Opto-thermal modelling for Need of investigation in new therapy techniques photo-thermal therapy. Mortality and side effects 2.1 Approach 2.2 Finite Element Modelling. Number of patients that can be trated 3. Experimental Results. Laser hyperthermia technique 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo Collaboration with a specialized Company in 4. Conclusions and Animal models Future Work - Good Laboratory Practices (GLP) - Qualified Staff - Ethical Committee Modelling and characterization of photothermal effects assisted with 3 gold nanorods in ex-vivo samples and in a murine model
  • 5. 0. General Index. 1. Introduction 1.2 The hyperthermia technique: the GOAL 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal Hyperthermia temperature Tumoral Cell death therapy. (from 42ºC to 65 ºC) 1.5 The Design. held during various minutes 2. Opto-thermal GOAL: 80% Tumour (3-10’) modelling for photo-thermal tissue ablation therapy. 2.1 Approach 2.2 Finite Element Modelling. 42 ºC – 65 ºC 3. Experimental Results. Tumour 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental 37 ºC Results – in-vivo 5-10 mm 4. Conclusions and Future Work Biological Tissue Hyperthermia temperature selected: 55 ºC ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA 4 CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
  • 6. 0. General Index. 1.2 The Hyperthermia Technique: State-of- 1. Introduction 1.1 The Motivation The-Art 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. Registro Tª 1.5 The Design. Láseres alta potencia estado sólido (Nd:YAG, OPO) 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach Radiofrecuencia 2.2 Finite Element Modelling. Ultrasonidos (HIFU) 3. Experimental Fibra óptica + Difusor Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Tumor Results – in-vivo 4. Conclusions and Tejido biológico Future Work - Low selectivity - Use high amounts of energy - Very expensive devices with big dimensions Modelling and characterization of photothermal effects assisted with 5 gold nanorods in ex-vivo samples and in a murine model
  • 7. 0. General Index. 1. Introduction 1.3 The Photo-thermal Therapy System 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology HIGH in Photo-thermal POWER therapy. LASER 1.5 The Design. DIODE 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Temperature Modelling. Register 3. Experimental Superficial Results. λ= 808 3.1 Experimental Set- nm up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo Nanoparticle Interna infusion: 4. Conclusions and Intratumoural or Future Work Intravenous ? Biological Tissue Modelling and characterization of photothermal effects assisted with 6 gold nanorods in ex-vivo samples and in a murine model
  • 8. 0. General Index. 1. Introduction 1.4 Nanotechnology in Photo-Thermal Therapy 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology Gold Nanoparticles GOLD NANORODS in Photo-thermal therapy. 1.5 The Design. Tuned optical EFFICIENCY POWER 2. Opto-thermal absorbance modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo Fig. adapted of “Cancer Research”, 69(9):1-9, (2009) 3.3 Experimental Results – in-vivo 1.5 - Passive A A Longitudinal 4. Conclusions and Surface Plasmon Future Work - Harmless 1 Absorción [cm -1] Resonance Peak B B Axial 0.5 Surface Plasmon Resonance Peak 0 400 500 600 700 800 900 1000 1100 Longitud de onda [nm] Modelling and characterization of photothermal effects assisted with 7 gold nanorods in ex-vivo samples and in a murine model
  • 9. 0. General Index. 1. Introduction 1.5 The Design: Experimental studies 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. Efficiency Study Efficacy Study 2.1 Approach 2.2 Finite Element Modelling. CT-26 COLON CANCER OPTIMIZE THE SET-UP 3. Experimental XENOGRAFT STUDIES Results. 3.1 Experimental Set- - Number of animales for group -> Statistics - Tumour size? up. 3.2 Experimental Results – ex-vivo - System design in terms of efficiency: - Stops Tumor growing? 3.3 Experimental Results – in-vivo (Power, Irradiance, Nanoparticle Concentration) - Ablation of the tumoral tissue? 4. Conclusions and - Therapy parameters Future Work (Exposure time, way of application) - Ethical Committee (international directives of animal handling) -> HEATING UP, NOT BURNING OR CHARRRING ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA 8 CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
  • 10. 0. General Index. 1. Introduction General Index: 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental 2. Opto-thermal Modelling for Results. 3.1 Experimental Set- up. 3.2 Experimental Photo-Thermal Therapy Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA 10 CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO
  • 11. 0. General Index. 1. Introduction 2.1 Approach 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. Energy Optical power, Temperature 1.5 The Design. Deposition Transferencia Irradiance Fuentes térmicas térmica 2. Opto-thermal P [W], I [W/cm2] modelling for photo-thermal therapy. Optical properties Physical and thermal properties 2.1 Approach of the tissue of the tissue 2.2 Finite Element Modelling. µa [cm-1], µs [cm-1] ρ[kg/m ]C [JKg-1K-1, k [Wm-1K-1], 3 3. Experimental Results. Thermal Source 3.1 Experimental Set- up. 3.2 Experimental Optical Power Results – ex-vivo 3.3 Experimental Thermal Energy Results – in-vivo Transferred Temp 4. Conclusions and Future Work dV dV Tissue absorption + Nanoparticles µtotal = µtissue+µnanoparticles Modelling and characterization of photothermal effects assisted with 11 gold nanorods in ex-vivo samples and in a murine model
  • 12. 0. General Index. 1. Introduction 2.2 Finite Element Modelling (FEM) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. - Less computational resources needed 1.4 Nanotechnology in Photo-thermal - It can be applied to complex geometries therapy. 1.5 The Design. 2. Opto-thermal modelling for Energetic Initial Thermal photo-thermal Contribution. Temperature Energy therapy. Laser energy 37 ºC transference 2.1 Approach absorption 2.2 Finite Element Modelling. 3. Experimental NO Results. 3.1 Experimental Set- Stop time Temperatures up. 3.2 Experimental reached? update Results – ex-vivo 3.3 Experimental Results – in-vivo YES 4. Conclusions and Future Work Final Temperature Modelling and characterization of photothermal effects assisted with 14 gold nanorods in ex-vivo samples and in a murine model
  • 13. 0. General Index. 1. Introduction General Index: 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental 3. Experimental Results Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work 15
  • 14. 0. General Index. 1. Introduction 3.1 Experimental Set-up (I) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Optoelectronic General Schema 1.4 Nanotechnology Thermocouple in Photo-thermal therapy. thermometer 1.5 The Design. Sonda termopar 2. Opto-thermal Lentes de hipodérmica modelling for photo-thermal Cabezal láser acoplo (HYP-1, Omega) Soporte therapy. (CNI-MDL-H-808-5000, CNI) d1 2.1 Approach 2.2 Finite Element Diámetro del haz Modelling. (FWHM) d0 3. Experimental Fibra óptica d2 Results. l1 l2 3.1 Experimental Set- (CNI-SMA-Fibre-600, CNI) up. 3.2 Experimental Results – ex-vivo l1 = l2 Tejido irradiado 3.3 Experimental f1= f2 = 2.54 cm Results – in-vivo D1 = D2= 2.54 cm Termómetro infrarrojo 4. Conclusions and (OS-530LE, Omega) Future Work Driver (PSU-H-LED, CNI) Modelling and characterization of photothermal effects assisted with 16 gold nanorods in ex-vivo samples and in a murine model
  • 15. 0. General Index. 1. Introduction 3.1 Experimental Set-up (II) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Experimental Set-up for therapy application in ex-vivo tissue samples 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work Modelling and characterization of photothermal effects assisted with 17 gold nanorods in ex-vivo samples and in a murine model
  • 16. 0. General Index. 1. Introduction 3.1 Experimental Set-up (and III) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Experimental set-up for therapy application in mice (in-vivo) 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work Modelling and characterization of photothermal effects assisted with 18 gold nanorods in ex-vivo samples and in a murine model
  • 17. 0. General Index. 3.1 Experimental Set-up: 1. Introduction 1.1 The Motivation Development Stages 1.2 The hyperthermia technique. 1.3 The Photo-thermal Develpment Stages of the Photo-Thermal Therapy System therapy system. 1.4 Nanotechnology in Photo-thermal therapy. Requirements 1.5 The Design. and Goals Optimization loop Optimization of the 2. Opto-thermal System modelling for photo-thermal therapy. 2.1 Approach Concept, Design Biological Model 2.2 Finite Element Experimental and Implementation ex-vivo Modelling. of the system (tissue samples) Results 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo Experimental Biological Model 3.3 Experimental in-vivo Results – in-vivo Results (ratones) 4. Conclusions and Future Work Optimization Clinical of the Application System (Human Beings) Modelling and characterization of photothermal effects assisted with 19 gold nanorods in ex-vivo samples and in a murine model
  • 18. 0. General Index. 1. Introduction 3.2 Experimental results - ex-vivo (I) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Sample preparation: 1.4 Nanotechnology in Photo-thermal - Fresh chicken muscle tissue. therapy. 1.5 The Design. - Previous marking for infrared thermometer alineation. 2. Opto-thermal modelling for - Hypodermical infusion of nanoparticles (Ntracker 30-PM-850, NANOPARTz, photo-thermal saline solution PH = 7.4, 0.1 ml, OD = 25). therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work Modelling and characterization of photothermal effects assisted with 20 gold nanorods in ex-vivo samples and in a murine model
  • 19. 0. General Index. 1. Introduction 3.2 Experimental results - ex-vivo (II) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Looking for the optimal irradiance, experimental results. 1.4 Nanotechnology in Photo-thermal therapy. 55 Pbeam = 1.25 W 1.5 The Design. Phaz = 0.5 W, IFWHM = 0.95 [W/cm2], Láser+NRds Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Láser+NRds 2. Opto-thermal 50 Phaz = 0.75 W, IFWHM = 1.43 [W/cm2], Láser+NRds IFWHM = 2.38 W/cm2 Phaz = 0.5 W, FWHM = 0.95 [W/cm2 Phaz = 1.00 W, IFWHM =I 1.90 [W/cm2], Láser+NRds ], Solo Láser modelling for 40 Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Láser+NRds 2 ΔT = 31 ºC 45 Phaz = 0.75 W, IFWHM = 1.43 [W/cm ], Solo Láser photo-thermal Phaz = 0.5 W, IFWHM = 0.95 [W/cm2], Solo Láser  T [ºC] therapy. 40 Phaz = 1.00 W, IFWHM = ], Solo Láser 2 Phaz = 0.75 W, IFWHM = 1.43 [W/cm21.90 [W/cm ], Solo Láser 35 2.1 Approach Phaz = 1.00 W, IFWHM = 1.90 [W/cm22.38 [W/cm2], Solo Láser Phaz = 1.25 W, IFWHM = ], Solo Láser 2.2 Finite Element 35 Phaz = 1.25 W, IFWHM = 2.38 [W/cm2], Solo Láser Modelling. 30 30 3. Experimental Results. 25 25 3.1 Experimental Set-  T [ºC] up. 20 3.2 Experimental 20 50 100 150 200 250 300 Results – ex-vivo Tiempo de exposición [sg] 3.3 Experimental Results – in-vivo 15 4. Conclusions and Future Work 10 ΔT = 3 ºC 5 0 0 50 100 150 200 250 300 Tiempo de exposición [sg] Exposure Time [s] Modelling and characterization of photothermal effects assisted with 22 gold nanorods in ex-vivo samples and in a murine model
  • 20. 0. General Index. 1. Introduction 3.3 Experimental Results - in-vivo (I) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. Animal model 1.4 Nanotechnology in Photo-thermal - Female mice, albines, BALB/c (BALB/cAnNHsd) , specific patogens free. therapy. 1.5 The Design. - Animals were handled by qualified staff in a company with the Good Laboratory Practice Certificate (GLP) 2. Opto-thermal modelling for Animal preparation photo-thermal therapy. - Random distribution by weigth. 2.1 Approach - Identification of each animal. 2.2 Finite Element Modelling. Identification - Hair removing from the exposed area. marks Shaving of 3. Experimental - Light anaesthesya Ketamine/Xilacine (10μl/g). irradiated area Results. 3.1 Experimental Set- - Hypodermic infusion of nanoparticles up. 3.2 Experimental (Gold Nanorods, Ntracker). Results – ex-vivo 3.3 Experimental - Laser irradiation exposure. Results – in-vivo 4. Conclusions and Positioning Future Work platform Laser beam direction 27 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 21. 0. General Index. 1. Introduction 3.3 Experimental Results - in-vivo (II) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal Study of the thermal increment induced as a function of laser irradiance. therapy system. 1.4 Nanotechnology in Photo-thermal Pbeam = 1.25 W therapy. 1.5 The Design. 35 IFWHM = 2.38 W/cm2 HYP: P = 0.5 W 2. Opto-thermal modelling for SUP: P = 0.5 W HYP: P = 1 W ΔT = 29.9 ºC 30 photo-thermal SUP: P = 1 W therapy. HYP: P = 1.25 W 2.1 Approach SUP: P = 1.25 W 25 2.2 Finite Element Modelling. 3. Experimental 20  T [ºC] Results. 3.1 Experimental Set- up. 3.2 Experimental 15 12 ºC Results – ex-vivo 3.3 Experimental Results – in-vivo 10 4. Conclusions and Future Work 5 0 0 50 100 150 200 240 Tiempo de exposición [sg] Exposure Time [s] 28 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 22. 0. General Index. 1. Introduction 3.3 Experimental Results - in-vivo (III) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal Proof of concept, Phaz = 1.25 W therapy system. experimental results. 1.4 Nanotechnology in Photo-thermal IFWHM = 2.38 W/cm2 therapy. 1.5 The Design. 60 T = 57.8 ºC 2. Opto-thermal modelling for 55 photo-thermal therapy. 2.1 Approach 2.2 Finite Element 50 Modelling. Temperatura [ºC] Temperature [ºC] 3. Experimental 45 Results. 3.1 Experimental Set- T = 38.1 ºC up. 40 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 35 4. Conclusions and HYP: Gold Nanorods + Láser Future Work SUP: Gold Nanorods + Láser 30 HYP: PBS + Láser SUP: PBS + Láser 25 0 100 200 300 400 500 600 Tiempo de exposición [sg] Exposure time [sg] 33 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 23. 0. General Index. 1. Introduction 3.3 Experimental Results - in-vivo (IV) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal Aspect of the skin after irradiation. therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for Skin exposed to the laser photo-thermal Superficiebeam expuesta de piel therapy. a la radiación láser 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental Results. 3.1 Experimental Set- up. 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work 34 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 24. 0. General Index. 1. Introduction 3.3 Experimental Results - in-vivo (V) 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal Proof of concept, FEM therapy system. 1.4 Nanotechnology Modelling. in Photo-thermal therapy. 1.5 The Design. 16 2. Opto-thermal 14 modelling for photo-thermal 12 therapy. 2.1 Approach 2.2 Finite Element 10 Modelling.  T [ºC] 3. Experimental 8 The superficial thermal gradient registered Results. 3.1 Experimental Set- experimentally was of 14.75 ºC, while the up. 3.2 Experimental 6 modelled one was of 14.86. This is an absolute Results – ex-vivo 3.3 Experimental 4 error less than 0.11 ºC (0.75 %) Results – in-vivo Superficial. Laser + NRds. EXP 4. Conclusions and 2 Superficial. Laser + NRds. FEM Future Work 0 0 100 200 300 400 500 600 Exposure exposición [sg] Tiempo de time [sg] 35 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 25. 0. General Index. 1. Introduction General Index: 1.1 The Motivation 1.2 The hyperthermia technique. 1.3 The Photo-thermal therapy system. 1.4 Nanotechnology in Photo-thermal therapy. 1.5 The Design. 2. Opto-thermal modelling for photo-thermal therapy. 2.1 Approach 2.2 Finite Element Modelling. 3. Experimental 4. Conclusions and future Results. 3.1 Experimental Set- up. 3.2 Experimental work Results – ex-vivo 3.3 Experimental Results – in-vivo 4. Conclusions and Future Work 37 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 26. 0. General Index. 1. Introduction 4.1 Conclusions: 1.1 Motivation 1.2 The hyperthermia technique 1.3 Photo-thermal The laser hyperthermia therapy system using gold nanoparticles therapy system. 1.4 Nanotechnology has been demonstrated to be VIABLE in a mice model. in Photo-thermal therapy. 1.5 Design. Only the tissue injected with nanoparticles reaches hyperthermia 2. Opto-thermal temperatures. modelling for photo-thermal therapy. 2.1 Approach The tissue exposed to the laser beam, but NO injected with 2.2 Energy Balance nanoparticles, remains unaltered (it does not reach hyperthermia 2.3 Implemention of the solution. FEM. 2.4 Finite Element temperature) Modelling. 3. Experimental The stablished irradiance does not induce tissue charring or skin Results. 3.1 Experimental Set- burning. up. 3.2 Experimental Results – ex-vivo 3.3 Experimental The computational model implemented allows to make accurate Results – in-vivo estimations of the final temperature of the irradiated tissue with 4. Conclusions and nanoparticles. Future Work 38 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 27. 0. General Index. 1. Introduction 4.2 Future work 1.1 Motivation 1.2 The hyperthermia technique 1.3 Photo-thermal Modelling and implementation therapy system. 1.4 Nanotechnology in Photo-thermal therapy. Study and design of new techniques of optical energy irradiation: 1.5 Design. contact applicators, more than one laser source, pulsed light. 2. Opto-thermal modelling for Design and test of an integrated control and monitorization photo-thermal therapy. system: 2.1 Approach Tissue Temp. 2.2 Energy Balance temperature register 2.3 Implemention of the solution. FEM. 2.4 Finite Element Modelling. Laser power 3. Experimental Results. 3.1 Experimental Set- up. Experimental study 3.2 Experimental Results – ex-vivo 3.3 Experimental Results – in-vivo Tumor model in mice to test the efficacy of the system 4. Conclusions and -Determine if the tumour growing is stopped and finally, the tumour is Future Work ablated. - 15 animals (BALB/c) - Cell line CT-26 mice colon cancer (CT26.WT) 39 Modelling and characterization of photothermal effects assisted with gold nanorods in ex-vivo samples and in a murine model
  • 28. Thank you for your attention! Have a nice day. ESTUDIO EXPERIMENTAL DE TÉCNICAS LÁSER PARA TERAPIA 40 CÁNCER EN RATONES UTILIZANDO NANOPARTÍCULAS DE ORO