A method to obtain the thermal parameters and the photothermal transduction efficiency in an optical hyperthermia device based on laser irradiation of gold nanoparticles
© Sánchez López de Pablo et al.; licensee Springer. 2014
Received: 31 March 2014
Accepted: 1 August 2014
Published: 27 August 2014
Optical hyperthermia systems based on the laser irradiation of gold nanorods seem to be a promising tool in the development of therapies against cancer. After a proof of concept in which the authors demonstrated the efficiency of this kind of systems, a modeling process based on an equivalent thermal-electric circuit has been carried out to determine the thermal parameters of the system and an energy balance obtained from the time-dependent heating and cooling temperature curves of the irradiated samples in order to obtain the photothermal transduction efficiency. By knowing this parameter, it is possible to increase the effectiveness of the treatments, thanks to the possibility of predicting the response of the device depending on the working configuration. As an example, the thermal behavior of two different kinds of nanoparticles is compared. The results show that, under identical conditions, the use of PEGylated gold nanorods allows for a more efficient heating compared with bare nanorods, and therefore, it results in a more effective therapy.
KeywordsGold nanoparticles Laser irradiation Optical hyperthermia Photothermal transduction efficiency Temperature curves Thermal parameters
Nanoscale materials have been broadly studied in recent years, thanks to their unique optical properties and their great potential in the development of biomedical applications. One of the most interesting areas is the use of plasmonic nanoparticles to enhance the diagnostic and treatment methods available for cancer. In this field, authors such as Letfullin and co-workers have recently described the optical properties, the kinetics of heating and cooling, and the spatial distribution of temperature of this kind of nanoparticles, providing a better understanding of these processes [1–3].
Specifically, rod-shaped gold nanoparticles, known as gold nanorods (GNRs), have a great potential because of their large light absorption and scattering cross sections in the near-infrared (NIR) region . Thanks to this optical behavior, GNRs are able to transform the absorbed energy into localized heat. This optical effect is used to develop cancer therapies as photothermal tumor destruction either by direct enough increase of temperature or indirectly by co-adjuvant drugs, at the same time delivered by the particle, or already present and activated by the heating [5–8].
Our research group has recently developed an optical hyperthermia device based on irradiation of GNRs with a continuous wave (CW) laser in order to induce in vitro death of human brain astrocytoma cells (1321 N1) . Unlike many high-energy pulsed lasers that generally lead to particle structure changes and ablation in a very short time, CW lasers allow heat dissipation from particles to surrounding medium (via phonon-phonon relaxation), so they are an appropriate choice in order to use the produced heat for the cure of cancer .
The effectiveness of the developed method was determined by measuring changes in cell viability after laser irradiation of cells in the presence of GNRs. In accordance to other results in comparable experiments [11–13], ours indicated that continuous laser irradiation in the presence of the particles induced a significant decrease in cell viability, while no decrease in cell viability was observed with laser irradiation or incubation with GNRs alone. Due to the limited capacity of laser penetration in tissues, this method could be used in clinical practice as an additional aid to surgery for removing brain tumors completely.
After this proof of concept, our objective was focused in getting a better understanding about the working principles and physical behavior of optical hyperthermia devices. It is not very common to find studies including a comprehensive characterization about the global phenomena in optical hyperthermia systems. Moreover, although now there are a huge variety of noble metal nanoparticles that can be used to carry out this kind of therapy, an absolute control about their behavior still does not exist. Therefore, it is necessary to develop a series of characterization and modeling processes to increase the effectiveness of the hyperthermia treatments, thanks to the prediction of the system response.
With this aim, a method to calculate the thermal parameters of the system and the photothermal transduction efficiency for different kinds of nanoparticles has been developed. This method, which allows an easy and effective thermal characterization and so predicts the thermal behavior of the system, is not only valid for our device but also for any kind of optical hyperthermia system.
Optical hyperthermia device
The CW laser (MDL H808, PSU-H-LED power source, Changchun New Industries, Changchun, China) works at 808 nm, with a maximum output power of 5 W, beam height from base of 29 nm, beam diameter at aperture of 5 to 8 mm, and dimensions of laser head of 155 × 77 × 60 mm3.
We have used two different kinds of commercial GNRs in order to compare their photothermal transduction efficiency. Both are tuned to the laser source and have their maximum surface plasmon resonance (SPR) at 808 nm (longitudinal band).
The first commercial GNRs used are bare GNRs (B-GNRs) A12-10-808-100 Nanorodz (Nanopartz, Salt Lake City, UT, USA). B-GNRs are dispersed in deionized water (DI-H2O) with <0.1% ascorbic acid and <0.1% cetyltrimethylammonium bromide (CTAB) surfactant capping agent. B-GNRs have an axial diameter of 10 nm and a length of 41 nm.
In this circuit, P is the delivered power, T(t) is the sample temperature which is time dependent, and C d (W/K) and C t (J/K) are the thermal conductance and the thermal capacitance of our experimental enclosure, respectively.
The resistor heats up the sample until the stabilization temperature (Tmax - m) is reached, and then, the voltage sample is shut off and the resistor is immediately removed from the sample in order to obtain the cooling curves (which correspond to the discharge curves of the capacitor) that characterize our experimental enclosure without the influence of the resistor that is still kept warm.
Thus, from a known power and from the values of τ and ΔT m experimentally obtained, we can calculate the thermal parameters (i.e., thermal capacitance and thermal conductance) that characterize the sample enclosure of the described optical hyperthermia device.
In this case, we chose a resistor of 15.2 Ω, the voltage source values were 1.5, 2.0, and 2.5 V, and the tested sample volumes were 500, 750, and 1,000 μl. We obtained three heating and cooling temperature curves for each possible configuration.
Photothermal transduction efficiency
From the Mie theory and taking into account different parameters such as the nanoparticle size and shape, the refractive index of the surrounding medium, and the laser wavelength, authors such as Zharov describe the optimal conditions for nanoparticles to obtain effective laser heating in optical hyperthermia applications .
On the other hand, we can find in the literature advanced models that completely describe the heat transfer behavior from the surface of nanoparticles presenting the heat sources produced by nanoparticles in the spherical volume of biological tissue [15, 16]. These methods allow for predicting the complete thermal response for applications to future cancer therapies as nanophotothermolysis and nanophotohyperthermia, but we propose a simpler approach in order to rapidly compare the photothermal response of nanoparticles in optical hyperthermia devices to be able to select those nanoparticles that allow us to obtain better results in each planned therapy.
In the previous expression (Equation 5), m and C p are the mass and the heat capacitance of each component of the irradiated sample, respectively, T is the temperature of the sample, Q I is the calorific energy that GNRs generate (energy source), Q0 is the baseline energy of the sample (represents the temperature rise of the sample due to the direct heating of the laser source), and Qext represents the energy flux transmitted out of the irradiated area.
In this expression (Equation 6), I is the power of the incident laser irradiation after the attenuation due to the different optical elements in the light path, η is the photothermal transduction efficiency (the parameter we want to calculate) that denotes a value for the efficacy of GNRs converting the incident light that interacts with them into thermal energy, and A λ is the optical density (also called absorbance) of the sample (colloidal dispersion) at the irradiation wavelength.
Once we know the heat transfer coefficient, it can be used to calculate the amount of energy that the sample accumulates or losses, from the temperature evolution.
In this case, we have estimated the value of η for the two kinds of nanorods described before (B-GNRs and PEG-GNRs). In both cases, the calculation was carried out from the temperature curves of three equal samples of water-dispersed GNRs with A λ = 1 (which corresponds with a concentration of 36 μg/ml) in order to obtain ΔT and from the temperature curves of three equal samples of deionized water to obtain Q0. All samples were irradiated with a laser power average of 2.0 W, and their volume was 500 μl.
Results and discussion
Then, the thermal conductance of our system could be estimated from the average of the thermal conductances obtained for each volume: Cd 1 (500 μl) = 0.052 W/K, Cd 2 (750 μl) = 0.052 W/K, and Cd 3 (1,000 μl) = 0.048 W/K so that C d ≈ 0.051 W/K.
Values of the average time constant τ i and thermal capacitance for each tested volume
C ti (J/K)
500 (i = 1)
750 (i = 2)
1,000 (i = 3)
In this case, we can observe that the values of thermal capacitance (expressed in J/K) have an increasing lineal evolution depending on the volume. This effect is consistent with the fact that the thermal capacitance is an extensive property, because their value depends on the amount of substance. Indeed, this parameter is defined as the ratio between the amount of thermal energy delivered to a body and the temperature change that the body experiments so that the greater is the volume, the lower is the experimented temperature change for a fixed amount of energy, and therefore, the greater is the value of the thermal capacitance.
Photothermal transduction efficiency
Once the thermal parameters have been calculated, to estimate the value of η, it is needed to know the percentage of the irradiation power (PLASER) incident on the sample (I) by taking into account the losses due to the light path through the optical elements between the output of the fiber and the sample. In this case, in the light path, there are a collimated lens and a 4-well plate. The lens has two faces and a percentage of losses of about 3%, and the 4-well plate adds a percentage of losses near 10% according to the manufacturers. Therefore, the total amount of losses is about 16%, and then, the incident power could be expressed as I = (1 - 0.16) PLASER.
Parameters and photothermal transduction efficiency obtained from samples of B-BNRs and PEG-GNRs (500 μl, A λ = 1, P LASER = 2.0 W)
From the observation of the previous graph, we can affirm that under the established conditions of experimentation, the photothermal transduction efficiency of PEG-GNRs is about 15% to 16% higher than in B-GNRs. Thus, under the described working conditions, the use of PEG-GNRs allow for a more efficient heating of the sample, and therefore, the use of this kind of nanoparticles results in a more effective therapy.
The estimation of the thermal parameters and the photothermal transduction efficiency allows us to compare the thermal behavior of different kinds of nanoparticles under similar working conditions. Moreover, it could be also useful to compare the thermal response of different kinds of nanoparticles under different working conditions as, for example, concentration, optical density, dispersion media, or sample holder. Therefore, the photothermal transduction efficiency is needed to determine the optimal conditions depending on each considered case.
To summarize, we can say that, from a series of input data to the system, as the power of irradiation and the optical density of the used nanoparticles, it is possible to calculate the photothermal transduction efficiency of these particles using the thermal parameters of the system and the temperature variation of the samples. Therefore, it is possible to determine, for any kind of gold nanoparticles (or other noble metals) with their peak of absorption syntonized with the wavelength of irradiation, the percentage of the optical power that interacts (absorption + scattering) with the sample that really becomes in a temperature increasing. The higher the value of this parameter, the higher the efficiency of the designed optical hyperthermia treatment, and so, if we know the value of this parameter previously, we could select those nanoparticles that allow us to obtain better results in the designed therapy.
The authors gratefully acknowledge the support of the Biomedical Research Networking Center.
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