High Therapeutic Efficiency of Magnetic Hyperthermia in Xenograft Models Achieved with Moderate Temperature Dosages in the Tumor Area

Abstract

PurposeTumor cells can be effectively inactivated by heating mediated by magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress inside the tumor remain to be identified. The present study investigates the therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC-3) xenografts in mice in vivo.MethodsSuperparamagnetic iron oxide nanoparticles, synthesized either via an aqueous (MF66; average core size 12 nm) or an organic route (OD15; average core size 15 nm) are analyzed in terms of their specific absorption rate (SAR), cell uptake and their effectivity in in vivo hyperthermia treatment.ResultsExceptionally high SAR values ranging from 658 ± 53 W*gFe−1 for OD15 up to 900 ± 22 W*gFe−1 for MF66 were determined in an alternating magnetic field (AMF, H = 15.4 kA*m−1 (19 mT), f = 435 kHz). Conversion of SAR values into system-independent intrinsic loss power (ILP, 6.4 ± 0.5 nH*m2*kg−1 (OD15) and 8.7 ± 0.2 nH*m2*kg−1 (MF66)) confirmed the markedly high heating potential compared to recently published data. Magnetic hyperthermia after intratumoral nanoparticle injection results in dramatically reduced tumor volume in both cancer models, although the applied temperature dosages measured as CEM43T90 (cumulative equivalent minutes at 43°C) are only between 1 and 24 min. Histological analysis of magnetic hyperthermia treated tumor tissue exhibit alterations in cell viability (apoptosis and necrosis) and show a decreased cell proliferation.ConclusionsConcluding, the studied magnetic nanoparticles lead to extensive cell death in human tumor xenografts and are considered suitable platforms for future hyperthermic studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-014-1417-0) contains supplementary material, which is available to authorized users.

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

“…MNP synthesis was performed by co-precipitation technique as described elsewhere. 29 The average core size of the MNPs was 12±3 nm, hydrodynamic diameter 85 nm, and specific absorption rate value 900 W/g Fe (corresponding to intrinsic loss power values of 8.7 nHm 2 *kg…”

“…The ζ-potential was −41 mV. 29 In vitro extrinsic hyperthermia (eh) PANC-1 and BxPC-3 cells were incubated for 60 minutes at different temperatures (41°C, 43°C, and 47°C). Temperatures were monitored using fiber optic temperature probe and thermometer (TS5 & FOTEMPMK-19; Optocon AG, Dresden, Germany).…”

“…Uptake of cellular MNP at 24 hours after incubation was quantified by atomic absorption spectroscopy (AAS 5 FL; Analytik Jena AG, Jena, Germany) as described elsewhere and was found to be of 22±6 pg Fe/cell (PANC-1) and 67±17 pg Fe/cell (BxPC-3), respectively, in a prototype experiment. 29 …”

Functionalization of Iron Oxide Magnetic Nanoparticles with the Multivalent Pseudopeptide N6l for Breast Tumor Targeting

“…DMSA coated iron oxide nanoparticles (MNP) were provided by Liquid Research LTD and obtained as previously described [26]. All reagents were purchased from Aldrich and used without further purification.…”

“…Three molecules have been previously described as targets of N6L: nucleolin, nucleophosmin, and sulfated glycosaminoglycans (GAGs), each with an affinity constant in the nanomolar range [25][26][27]. We first evaluated the ability of MNP-N6L to recognize nucleolin.…”