Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal’s surface. The results indicate that temperature errors as large as 7 ∘ C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

Magnetic nanoparticle hyperthermia consists of an increase of the temperature of magnetic nanoparticles (heat centres) due to the interaction of their magnetic moments with an alternating magnetic field. In vivo experiments using this method usually use a few fibre-optic thermometers inserted in the animal body to monitor the heat deposition. As a consequence, only a few points of the 3D temperature distribution can be monitored by this invasive procedure. It is the purpose of this work to show that non-invasive infrared thermography is able to detect, in real time, magnetic nanoparticle hyperthermia as well as monitor the harmful field-induced eddy currents in a murine model with a subcutaneous tumour. This surface temperature measurement method has the potential to give information about the intratumoral temperature. The non-invasive magnetic hyperthermia experiments were performed at 300 kHz in non-uniform field configuration conditions in healthy mice and murine tumour induced by sarcoma S180. A soft ferrite-based biocompatible magnetic colloid consisting of manganese-ferrite nanoparticles surface-coated with citric acid were used in the experiments, which were extensively characterised by several techniques (transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM)). The amplitude of the alternating magnetic fields was obtained from measurements using an AC field probe at similar experimental conditions. The temperature measurements were obtained from an infrared thermal camera and a fibre-optic thermometer. Three-minute magnetic hyperthermia experiments revealed surface temperature increase as high as 11 °K in healthy and (5 °K in S180 tumour) animals when injecting subcutaneously 2 mg of magnetic nanoparticles (86 μL of magnetic fluid), in contrast to around 1.5 °K (for healthy) and 2.5 °K (for cancerous) animals in experiments without the colloid due to field-induced eddy currents at the animal surface. The thermographic temperature measurements were found to agree with the fibre-optic measurements within a 5% error, and were associated with the skin emissivity angle of dependence in the experimental set-up. On the other hand, a 30-min magnetic nanoparticle hyperthermia revealed surface temperature increases as high as 12 °K close to the injection site, while above 2-3 cm no significant temperature increase was observed. Curiously, the intratumoral temperature, monitored by a fibre-optic sensor, was found to be almost the same as the thermal camera surface temperature after achieving an equilibrium temperature regime. From the observed isotherms at the animal surface, using an analytical heat conduction model, taking into account surface conductance, we estimate a magnetic heating power of 0.45 W/cm(3) and a specific loss power (SLP) of 85 W/g for a field of the order of only 10 kA/m at the injection site region. The results indicate that infrared thermography may be a promising tool for both early cancer detection and for hyperthermia treatment (at least for subcutaneous tumours), since the method permits access to information about the intratumoral temperature during a real-time magnetic hyperthermia as well as to estimate the in vivo nanoparticles SLP.

Over the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC₅₀ values ranging from 22.53 µM to 50.18 µM, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)]PF₆ complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas.

Infection caused by the new coronavirus (SARS-CoV-2) has become a serious worldwide public health problem, and one of the most important strategies for its control is mass testing. Loop-mediated isothermal amplification (LAMP) has emerged as an important alternative to simplify the diagnostics of infectious diseases. In addition, an advantage of LAMP is that it allows for easy reading of the final result through visual detection. However, this step must be performed with caution to avoid contamination and false-positive results. LAMP performed on microfluidic platforms can minimize false-positive results, in addition to having potential for point-of-care applications. Here, we describe a polystyrene-toner (PS-T) centrifugal microfluidic device manually controlled by a fidget spinner for molecular diagnosis of COVID-19 by RT-LAMP, with integrated and automated colorimetric detection. The amplification was carried out in a microchamber with 5 μL capacity, and the reaction was thermally controlled with a thermoblock at 72 °C for 10 min. At the end of the incubation time, the detection of amplified RT-LAMP fragments was performed directly on the chip by automated visual detection. Our results demonstrate that it is possible to detect COVID-19 in reactions initiated with approximately 10⁻³ copies of SARS-CoV-2 RNA. Clinical samples were tested using our RT-LAMP protocol as well as by conventional RT-qPCR, demonstrating comparable performance to the CDC SARS-CoV-2 RT-qPCR assay. The methodology described in this study represents a simple, rapid, and accurate method for rapid molecular diagnostics of COVID-19 in a disposable microdevice, ideal for point-of-care testing (POCT) systems.