Abstract

Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimally invasive tool for localized tumor treatment by sensitizing or killing tumor cells with the help of thermal stress. Therefore, the selection of MNP exhibiting a sufficient heating capacity (specific absorption rate, SAR) to achieve satisfactory temperatures in vivo is necessary. Up to now, the SAR of MNP is mainly determined using ferrofluidic suspensions and may distinctly differ from the SAR in vivo due to immobilization of MNP in tissues and cells. The aim of our investigations was to study the correlation between the SAR and the degree of MNP immobilization in dependence of their physicochemical features.In this study, the included MNP exhibited varying physicochemical properties and were either made up of single cores or multicores. Whereas the single core MNP exhibited a core size of approximately 15 nm, the multicore MNP consisted of multiple smaller single cores (5 to 15 nm) with 65 to 175 nm diameter in total. Furthermore, different MNP coatings, including dimercaptosuccinic acid (DMSA), polyacrylic acid (PAA), polyethylenglycol (PEG), and starch, wereinvestigated. SAR values were determined after the suspension of MNP in water. MNP immobilization in tissues was simulated with 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels.The highest SAR values were observed in ferrofluidic suspensions, whereas a strong reduction of the SAR after the immobilization of MNP with PVA was found. Generally, PVA embedment led to a higher immobilization of MNP compared to immobilization in agarose gels. The investigated single core MNP exhibited higher SAR values than the multicore MNP of the same core size within the used magnetic field parameters. Multicore MNP manufactured via different synthesis routes (fluidMAG-D, fluidMAG/12-D) showed different SAR although they exhibited comparable core and hydrodynamic sizes. Additionally, no correlation between ζ-potential and SAR values after immobilization was observed.Our data show that immobilization of MNP, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNP are immobilized in cells and tissues. This aspect should be adequately considered when determining the SAR of MNP for magnetic hyperthermia.

Highlights

  • Up to now, a huge variation range of magnetic nanoparticle (MNP) formulations have been proposed for magnetic hyperthermia applications

  • Our investigations showed a clear reduction of specific absorption rates (SAR) values after immobilization in 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels in comparison to fluidic samples for all investigated MNP types when using defined alternating magnetic field (AMF) conditions (H = 15.4 kA/m, f = 435 kHz)

  • Our investigation showed that the SAR of MNP in fluidic and immobilized state is only influenced by the specific characteristics of the MNP core including core structure and core size

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Summary

Introduction

A huge variation range of magnetic nanoparticle (MNP) formulations have been proposed for magnetic hyperthermia applications. Magnetic hyperthermia is characterized by the production of heat by exposure of the target tissues, previously loaded with MNP, to an alternating magnetic field (AMF) due to magnetization reversal losses [1,2]. There is a necessity of selecting MNP which display high specific absorption rates (SAR) and which are able to generate temperatures above 43°C to efficiently eradicate tumor cells and sensitize them for chemotherapy and/or radiation therapy [3,4,5]. A common technique to determine the SAR of MNP is the use of calorimetric methods. In this context, MNP are exposed to an AMF and the generation of heat in dependence of the amount of the sample’s iron content is determined. To allow the comparison of SAR values independent of the characteristics of the used AMF, consideration of the intrinsic loss power (ILP) has been suggested [6]

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