Structural properties of magnetic nanoparticles determine their heating behavior - an estimation of the in vivo heating potential

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, were investigated. 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.

Agglomeration of magnetic nanoparticles and its effects on magnetic hyperthermia

“…This phenomenon was also reported in literature, where a decrease in SLP of approx. 20 % was found upon immobilization [15]. Investigation with other measurement techniques, such as AC magnetic susceptibility, confirm a reduction of Brownian relaxation for MNP immobilized inside cells [16].…”

Magnetic thermoablation stimuli alter BCL2 and FGF-R1 but not HSP70 expression profiles in BT474 breast tumors

“…The hrTeM micrograph was prepared as described elsewhere. 37 International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 34.215.51.103 on 11-May-2018 For personal use only.…”

Means to increase the therapeutic efficiency of magnetic heating of tumors

“…Taken together, this means that immobilization of MNPs, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNPs are sticking to cells and tissues [25].…”

“…The lack of a lymphatic system in tumors is additionally expected to improve nanoparticle retention in tumors. To facilitate their extravasation from the vascular system into the tumor interstitium, MNPs should be smaller than 200 and 400 nm [26], a requirement that counteracts with the specifications for MNPs with higher heating potential [25].…”

“…During the exposure to an alternating magnetic field, the magnetization vector of the MNPs with diameters smaller than 40 nm -together with distinct magnetic field parameters -will relax according to the direction of the applied external alternating magnetic field (Neél relaxation) and/or the whole MNP will rotate (Brown relaxation) [4]. The heating capability (the so-called heating potential) of the magnetic material will strongly depend upon its structural features, such as size, shape, and microstructure, and the features of the external magnetic field [25].…”