Fabrication and characterization of a novel magnetic nanostructure based on pectin-cellulose hydrogel for in vitro hyperthermia during cancer therapy.

Herein, a new magnetic nanobiocomposite based on a synthesized cross-linked pectin-cellulose hydrogel (cross-linked Pec-Cel hydrogel) substrate was designed and synthesized. The formation of the cross-linked Pec-Cel hydrogel with a calcium chloride agent and its magnetization process caused a new and efficient magnetic nanobiocomposite. Several spectral and analytical techniques, including FTIR, SEM, VSM, TGA, XRD, and EDX analyses, were performed to confirm and characterize the structural features of the magnetic cross-linked pectin-cellulose hydrogel nanobiocomposite (magnetic cross-linked Pec-Cel hydrogel nanobiocomposite). Based on SEM images, prepared Fe3O4 magnetic nanoparticles (MNPs) were uniformly dispersed in the Pec-Cel hydrogel context, representing an average particle size between 50.0 and 60.0 nm. The XRD pattern also confirms the crystallinity of the magnetic nanobiocomposite. All constituent elements and their distribution have been depicted in the EDX analysis of the magnetic nanobiocomposite. VSM curves confirmed the superparamagnetic behavior of Fe3O4 MNPs and the magnetic nanobiocomposite with a saturation magnetization of 77.31 emu g-1 and 48.80 emu g-1, respectively. The thermal stability of the nanobiocomposite was authenticated to ca. 800 °C based on the TGA thermogram. Apart from analyzing the structural properties of the magnetic cross-linked Pec-Cel hydrogel nanobiocomposite, different concentrations (0.5 mg mL-1, 1.0 mg mL-1, 2.0 mg mL-1, 5.0 mg mL-1, and 10.0 mg mL-1) of this new magnetic nanostructure were exposed to an alternating magnetic field (AMF) at different frequencies (100.0 MHz, 200.0 MHz, 300.0 MHz, and 400.0 MHz) to evaluate its capacity for an in vitro hyperthermia process; in addition, the highest specific absorption rate (126.0 W g-1) was obtained by the least magnetic nanobiocomposite concentration (0.5 mg mL-1).

Investigation of crystalline lens overshooting: ex vivo experiment and optomechanical simulation results.

Introduction: Crystalline lens overshooting refers to a situation in which the lens momentarily shifts too much from its typical location immediately after stopping the rotational movement of the eye globe. This movement can be observed using an optical technique called Purkinje imaging. Methods: In this work, an experimental setup was designed to reproduce this effect ex vivo using a fresh porcine eye. The sample was rotated 90° around its centroid using a high-velocity rotation stage, and the Purkinje image sequences were recorded, allowing us to quantify the overshooting effect. The numerical part of the study consisted of developing a computational model of the eye, based on the finite element method, that allowed us to understand the biomechanical behavior of the different tissues in this dynamic scenario. A 2D fluid-structure interaction model of the porcine eye globe, considering both the solid parts and humors, was created to reproduce the experimental outcomes. Results: Outputs of the simulation were analyzed using an optical simulation software package to assess whether the mechanical model behaves optically like the real ex vivo eye. The simulation predicted the experimental results by carefully adjusting the mechanical properties of the zonular fibers and the damping factor. Conclusion: This study effectively demonstrates the importance of characterizing the dynamic mechanical properties of the eye tissues to properly comprehend and predict the overshooting effect.

FEM thermal assessment of a 3-D irregular tumor with capillaries in magnetic nanoparticle hyperthermia via dissimilar injection points.

In this study, simulation of magnetic nanoparticle hyperthermia is performed on a 3D tumor model constructed based on a CT image of a tumor. In the first step, magnetic nanoparticles are injected into two points of the tumor tissue with the same parameters. Results show that temperature profiles in the vicinity of the injection points are not similar due to the presence of blood capillaries. Therefore, the effects of using dissimilar injection parameters for the two injection points on the heating pattern and damage fraction of the tumor are investigated. The results demonstrate that using dissimilar values for injection parameters such as injection rate, injection time, and nanofluid volume fraction is a way to achieve a higher damage fraction of the tumor cells, but, the asynchronous injections strategy does not lead to more significant damage to the tumor. None of the cases showed significant improvement in the uniformity of the temperature distribution, suggesting that conducting injections under the same conditions is the best way to create an almost uniform temperature profile. The numerical simulation validation results also advocate the accuracy of the model used in this study. This research can serve as a guide for designing parameters for future studies.

Simulation of heat transfer, mass transfer and tissue damage in magnetic nanoparticle hyperthermia with blood vessels.

Numerical simulation of magnetic nanoparticle hyperthermia for cancer treatment has been investigated in this study. The presented simulation did account for the effects of fluid flow, mass flow, and heat transfer during the MNP hyperthermia. The tumor was assumed to be a porous slab, 30% of which had been necrosed previously, with two capillaries, where magnetic nanoparticles were added into the bloodstream and distributed in the tumor by blood flow through capillaries. Fluid flow, mass transfer by capillaries, and interstitial tissues have been coupled in this study. Furthermore, tumor tissue damage has been calculated using a thermal damage indicator. The goal of this research is to find an optimum injection duration and exposure time in order to maximize hyperthermia treatment effectiveness using the BOBYQA optimization method. At the end of the 1-h time hyperthermia treatment, most of the non-necrotic tissue of the tumor were damaged. Moreover, the fraction of damaged tissue increased to more than 90% in some parts of the tumor. Results of this study indicate that MNP hyperthermia with the proposed setup can effectively damage the tumor in just one session, making it more susceptible to complementary therapies such as radiotherapy or chemotherapy.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy.

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.