A Step Forward for the Treatment of Localized Prostate Cancer Using Gold Nanoparticles Combined with Laser Irradiation.

Prostate cancer (PCA) is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide. The conventional treatments available are beneficial to only a few patients and, in those, some present adverse side effects that eventually affect the quality of life of most patients. Thus, there is an urgent need for effective, less invasive and targeted specific treatments for PCA. Photothermal therapy (PTT) is a minimally invasive therapy that provides a localized effect for tumour cell ablation by activating photothermal agents (PTA) that mediate the conversion of the light beam's energy into heat at the site. As tumours are unable to easily dissipate heat, they become more susceptible to temperature increases. In the PTT field, gold nanoparticles (AuNPs) have been attracting interest as PTA. The aim of this study was to formulate AuNPs capable of remaining retained in the tumour and subsequently generating heat at the tumour site. AuNPs were synthesized and characterized in terms of size, polydispersity index (PdI), zeta potential (ZP), morphology and the surface plasmon resonance (SPR). The safety of AuNPs and their efficacy were assessed using in vitro models. A preliminary in vivo safety assessment of AuNPs with a mean size lower than 200 nm was confirmed. The morphology was spherical-like and the SPR band showed good absorbance at the laser wavelength. Without laser, AuNPs proved to be safe both in vitro (>70% viability) and in vivo. In addition, with laser irradiation, they proved to be relatively effective in PCA cells. Overall, the formulation appears to be promising for use in PTT.

Rational approach to design gold nanoparticles for photothermal therapy: the effect of gold salt on physicochemical, optical and biological properties.

Among the unique characteristics associated to gold nanoparticles (AuNPs) in biomedicine, their ability to convert light energy into heat opens ventures for improved cancer therapeutic options, such as photothermal therapy (PTT). PTT relies on the local hyperthermia of tumor cells upon irradiation with light beams, and the association of AuNPs with radiation within the near infrared (NIR) range constitutes an advantageous strategy to potentially improve PTT efficacy. Herein, it was explored the effect of the gold salt on the AuNPs' physicochemical and optical properties. Mostly spherical-like negatively charged AuNPs with variable sizes and absorbance spectra were obtained. In addition, photothermal features were assessed using in vitro phantom models. The best formulation showed the ability to increase their temperature in aqueous solution up to 19 °C when irradiated with a NIR laser for 20 min. Moreover, scanning transmission electron microscopy confirmed the rearrangement of the gold atoms in a face-centered cubic structure, which further allowed to calculate the photothermal conversion efficiency upon combination of theoretical and experimental data. AuNPs also showed local retention after being locally administered in in vivo models. These last results obtained by computerized tomography allow to consider these AuNPs as promising elements for a PTT system. Moreover, AuNPs showed high potential for PTT by resulting in in vitro cancer cells' viability reductions superior to 70 % once combine with 5 min of NIR irradiation.

Biological Thermal Performance of Organic and Inorganic Aerogels as Patches for Photothermal Therapy.

Aerogels are materials with unique properties, among which are low density and thermal conductivity. They are also known for their exquisite biocompatibility and biodegradability. All these features make them attractive for biomedical applications, such as their potential use in photothermal therapy (PTT). This technique is, yet, still associated with undesirable effects on surrounding tissues which emphasizes the need to minimize the exposure of healthy regions. One way to do so relies on the use of materials able to block the radiation and the heat generated. Aerogels might be potentially useful for this purpose by acting as insulators. Silica- and pectin-based aerogels are reported as the best inorganic and organic thermal insulators, respectively; thus, the aim of this work relies on assessing the possibility of using these materials as light and thermal insulators and delimiters for PTT. Silica- and pectin-based aerogels were prepared and fully characterized. The thermal protection efficacy of the aerogels when irradiated with a near-infrared laser was assessed using phantoms and ex vivo grafts. Lastly, safety was assessed in human volunteers. Both types presented good textural properties and safe profiles. Moreover, thermal activation unveils the better performance of silica-based aerogels, confirming the potential of this material for PTT.

The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment.

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer.

A Comprehensive Updated Review on Magnetic Nanoparticles in Diagnostics.

Magnetic nanoparticles (MNPs) have been studied for diagnostic purposes for decades. Their high surface-to-volume ratio, dispersibility, ability to interact with various molecules and superparamagnetic properties are at the core of what makes MNPs so promising. They have been applied in a multitude of areas in medicine, particularly Magnetic Resonance Imaging (MRI). Iron oxide nanoparticles (IONPs) are the most well-accepted based on their excellent superparamagnetic properties and low toxicity. Nevertheless, IONPs are facing many challenges that make their entry into the market difficult. To overcome these challenges, research has focused on developing MNPs with better safety profiles and enhanced magnetic properties. One particularly important strategy includes doping MNPs (particularly IONPs) with other metallic elements, such as cobalt (Co) and manganese (Mn), to reduce the iron (Fe) content released into the body resulting in the creation of multimodal nanoparticles with unique properties. Another approach includes the development of MNPs using other metals besides Fe, that possess great magnetic or other imaging properties. The future of this field seems to be the production of MNPs which can be used as multipurpose platforms that can combine different uses of MRI or different imaging techniques to design more effective and complete diagnostic tests.

Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.

The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.

Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward.

Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues' temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC's specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future.

A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach.

Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors' etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650-900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.

Nightside condensation of iron in an ultrahot giant exoplanet.

Ultrahot giant exoplanets receive thousands of times Earth's insolation1,2. Their high-temperature atmospheres (greater than 2,000 kelvin) are ideal laboratories for studying extreme planetary climates and chemistry3-5. Daysides are predicted to be cloud-free, dominated by atomic species6 and much hotter than nightsides5,7,8. Atoms are expected to recombine into molecules over the nightside9, resulting in different day and night chemistries. Although metallic elements and a large temperature contrast have been observed10-14, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ('evening') and night-to-day ('morning') terminators could, however, be revealed as an asymmetric absorption signature during transit4,7,15. Here we report the detection of an asymmetric atmospheric signature in the ultrahot exoplanet WASP-76b. We spectrally and temporally resolve this signature using a combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11 ± 0.7 kilometres per second on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside16. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. We conclude that iron must therefore condense during its journey across the nightside.

Probing deep tissues with laser-induced thermotherapy using near-infrared light.

Optically tunable gold nanoparticles have been widely used in research with near-infrared light as a means to enhance laser-induced thermal therapy since it capitalizes on nanoparticles' plasmonic heating properties. There have been several studies published on numerical models replicating this therapy in such conditions. However, there are several limitations on some of the models which can render the model unfaithful to therapy simulations. In this paper, two techniques of simulating laser-induced thermal therapy with a high-absorbing localized region of interest inside a phantom are compared. To validate these models, we conducted an experiment of an agar-agar phantom with an inclusion reproducing it with both models. The phantom was optically characterized by absorption and total attenuation. The first model is based on the macroperspective solution of the radiative transfer equation given by the diffusion equation, which is then coupled with the Pennes bioheat equation to obtain the temperature. The second is a Monte Carlo model that considers a stochastic solution of the same equation and is also considered as input to the Pennes bioheat transfer equation which is then computed. The Monte Carlo is in good agreement with the experimental data having an average percentage difference of 4.5% and a correlation factor of 0.98, while the diffusion method comparison with experimental data is 61% and 0.95 respectively. The optical characterization of the phantom and its inclusion were also validated indirectly since the Monte Carlo, which used those parameters, was also validated. While knowing the temperature in all points inside a body during photothermal therapy is important, one has to be mindful of the model which fits the conditions and properties. There are several reasons to justify the discrepancy of the diffusion method: low-scattering conditions, absorption, and reduced scattering are comparable. The error bars that are normally associated when characterizing an optical phantom can justify also a part of that uncertainty. For low-size tumors in depth, one may have to increase the light dosage in photothermal therapies to have a more effective treatment.

Optical eye simulator for laser dazzle events.

An optical simulator of the human eye and its application to laser dazzle events are presented. The simulator combines optical design software (ZEMAX) with a scientific programming language (MATLAB) and allows the user to implement and analyze a dazzle scenario using practical, real-world parameters. Contrary to conventional analytical glare analysis, this work uses ray tracing and the scattering model and parameters for each optical element of the eye. The theoretical background of each such element is presented in relation to the model. The overall simulator's calibration, validation, and performance analysis are achieved by comparison with a simpler model based uponCIE disability glare data. Results demonstrate that this kind of advanced optical eye simulation can be used to represent laser dazzle and has the potential to extend the range of applicability of analytical models.

3D finite element model for writing long-period fiber gratings by CO2 laser radiation.

In the last years, mid-infrared radiation emitted by CO2 lasers has become increasing popular as a tool in the development of long-period fiber gratings. However, although the development and characterization of the resulting sensing devices have progressed quickly, further research is still necessary to consolidate functional models, especially regarding the interaction between laser radiation and the fiber's material. In this paper, a 3D finite element model is presented to simulate the interaction between laser radiation and an optical fiber and to determine the resulting refractive index change. Dependence with temperature of the main parameters of the optical fiber materials (with special focus on the absorption of incident laser radiation) is considered, as well as convection and radiation losses. Thermal and residual stress analyses are made for a standard single mode fiber, and experimental results are presented.

Application of schlieren interferometry to temperature measurements during laser welding of high-density polyethylene films.

Schlieren interferometry is found to be an alternative tool for temperature measurement during thermoplastic laser welding with regard to methods based on thermocouples or optical pyrometers. In fact, these techniques are not easily applied when materials to be processed have reduced thickness, negligible heat conduction, and low emissivity, as is the case of welding high-density polyethylene films with 10.6-microm CO2 laser radiation, even if the method reaches its applicability limit after approximately 1 s of the interaction process. The schlieren method provides the means and the results to probe the thermal variations of the laser-thermoplastic interaction on both the surface and the interface between the sample material and the air.