Cell-Promoted Nanoparticle Aggregation Decreases Nanoparticle-Induced Hyperthermia under an Alternating Magnetic Field Independently of Nanoparticle Coating, Core Size, and Subcellular Localization

Abstract

Magnetic hyperthermia has a significant potential to be a new breakthrough for cancer treatment. The simple concept of nanoparticle-induced heating by the application of an alternating magnetic field has attracted much attention, as it allows the local heating of cancer cells, which are considered more susceptible to hyperthermia than healthy cells, while avoiding the side effects of traditional hyperthermia. Despite the potential of this therapeutic approach, the idea that local heating effects due to the application of alternating magnetic fields on magnetic nanoparticle-loaded cancer cells can be used as a treatment is controversial. Several studies indicate that the heating capacity of magnetic nanoparticles is largely reduced in the cellular environment due to increased viscosity, aggregation and dipolar interactions. However, an increasing number of studies, both in vitro and in vivo, show evidence of successful magnetic hyperthermia treatment on several different types of cancer cells. This apparent contradiction might be due to the use of different experimental conditions. Here we analyze the effects of several parameters on the cytotoxic efficiency of magnetic nanoparticles as heat inductors under an alternating magnetic field. Our results indicate that cell-nanoparticle interaction reduces the cytotoxic effects of magnetic hyperthermia, independently of nanoparticle coating and core size, the cell line used and the subcellular localization of nanoparticles. However, there seems to occur a synergistic effect between the application of an external source of heat and the presence of magnetic nanoparticles, leading to higher toxicities than those induced by heat alone, or the accumulation of nanoparticles within cells.

Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with αvβ3-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death

“…This effect has been attributed to Brownian mobility restriction 16,17 , or particle aggregation 18 , including also the detrimental effect of viscosity on the obtained SAR 19 . In previous studies conducted in our laboratory it has been observed that the inefficiency of the NPs to respond to AMF is due to the compaction of NPs as large aggregates with random NPs orientation in the lysosomes of Pan 02 tumor cells 20 . In contrast, several groups have recently reported cell death after MHT treatment but with disagreements about perceptible changes or not in temperature during the treatment [21][22][23] .…”

Nanocomposite Polymer Scaffolds Responding under External Stimuli for Drug Delivery and Tissue Engineering Applications

“…The heating efficiency of an ensemble of magnetic NPs depends not only on the structural and magnetic properties of NPs but also on the magnitude and frequency of the applied magnetic field, the media viscosity, and NPs concentration and aggregation state . Therefore, IO NPs displaying high heating power are currently available for MH.…”

Applications of superparamagnetic iron oxide nanoparticles in drug and therapeutic delivery, and biotechnological advancements

“…Cell endocytosis, retention, and exocytosis become very important when nanoparticles are used for various types of treatments. There are reports of a reduced hyperthermia effect when nanoparticles are located in endosomes, and reports of spontaneous endosomal escape [ 113 – 114 ]. For the specific treatment of cisplatin-resistant nasopharyngeal carcinoma, Weng et al [ 115 ] produced SPIONs covered with cisplatin and with TAT peptide (a HIV-derived cell penetrating peptide).…”