Critical Parameters to Improve Pancreatic Cancer Treatment Using Magnetic Hyperthermia: Field Conditions, Immune Response, and Particle Biodistribution

Abstract

Magnetic hyperthermia (MH) was used to treat a murine model of pancreatic cancer. This type of cancer is generally characterized by the presence of dense stroma that acts as a barrier for chemotherapeutic treatments. Several alternating magnetic field (AMF) conditions were evaluated using three-dimensional (3D) cell culture models loaded with magnetic nanoparticles (MNPs) to determine which conditions were producing a strong effect on the cell viability. Once the optimal AMF conditions were selected, in vivo experiments were carried out using similar frequency and field amplitude parameters. A marker of the immune response activation, calreticulin (CALR), was evaluated in cells from a xenograft tumor model after the MH treatment. Moreover, the distribution of nanoparticles within the tumor tissue was assessed by histological analysis of tumor sections, observing that the exposure to the alternating magnetic field resulted in the migration of particles toward the inner parts of the tumor. Finally, a relationship between an inadequate body biodistribution of the particles after their intratumoral injection and a significant decrease in the effectiveness of the MH treatment was found. Animals in which most of the particles remained in the tumor area after injection showed higher reductions in the tumor volume growth in comparison with those animals in which part of the particles were found also in the liver and spleen. Therefore, our results point out several factors that should be considered to improve the treatment effectiveness of pancreatic cancer by magnetic hyperthermia.

Smart Modification on Magnetic Nanoparticles Dramatically Enhances Their Therapeutic Properties

“…Considering all the information reported, we will expect advantages to using MNP-GEM in comparison with GEM in an in vivo pancreatic cancer model. There are reports in the literature where MNP have been tested in vivo in subcutaneous and xenograft mouse models of pancreatic cancer [13,14,19,69,70]. In the studies wherein the nanoparticles are intratumorally injected [13,14,19], the results highlight the good biocompatibility of ironoxide-based formulations and the efficacy of hyperthermia treatment with high loads of the particles.…”

“…There are reports in the literature where MNP have been tested in vivo in subcutaneous and xenograft mouse models of pancreatic cancer [13,14,19,69,70]. In the studies wherein the nanoparticles are intratumorally injected [13,14,19], the results highlight the good biocompatibility of ironoxide-based formulations and the efficacy of hyperthermia treatment with high loads of the particles. However, it is also common to observe the biodistribution of the particles also in the liver and spleen.…”

“…Hence, using smart nanoparticles could overcome the shortcomings of traditional chemotherapy, such as the lack of specificity and side effects [8,9]. In this sense, magnetic nanoparticles have been widely studied [10][11][12][13]. They can be used as a diagnostic tool in magnetic resonance imaging (MRI), promote cancer cell death via magnetic hyperthermia (MH), which involves the generation of heat when an alternating magnetic field (AMF) is applied [10,[14][15][16], and also as carriers of anticancer drugs [17][18][19].…”

“…They can be used as a diagnostic tool in magnetic resonance imaging (MRI), promote cancer cell death via magnetic hyperthermia (MH), which involves the generation of heat when an alternating magnetic field (AMF) is applied [10,[14][15][16], and also as carriers of anticancer drugs [17][18][19]. Despite all the efforts done to understand the mechanisms involved in cell death and to improve the therapeutic efficacy of MNP [10,13], a comprehensive report on cell-nanoparticle interactions is needed.…”

Numerical Investigation of Ferrofluid Preparation during In-Vitro Culture of Cancer Therapy for Magnetic Nanoparticle Hyperthermia

“…Magnetic nanoparticle (MNP) hyperthermia has a great deal of potential for cancer therapy because of its effectiveness and minimal invasive effects on the healthy tissues surrounding the tumor [ 1 , 2 , 3 ]. In this therapy, the malignant tissues are damaged with the help of the targeted heat induction caused by nanoparticles in the presence of an alternating current (AC) magnetic field [ 4 , 5 , 6 ].…”