Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.</jats:p></jats:sec>

Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma

“…These targeted temperatures are chosen since they lead to efficient magnetic hyperthermia treatment of various cancers (glioma, lymphoma, melanoma and carcinoma) without causing serious damage in healthy surrounding tissues, 19 , 20 , 21 , 22 . Comparison between M-PLL and IONPs efficacy is carried out, 23 , 24 , 25 , by taking into consideration the strength of the magnetic field needed to reach an intratumor temperature of 43-46 °C, the number of mice requiring a second nanoparticle administration to re-activate the treatment, nanoparticle and temperature intratumor distributions, the decrease in tumor volume following treatments, and the percentage of fully cured mice.…”

In vivo magnetic nanoparticle hyperthermia: a review on preclinical studies, low-field nano-heaters, noninvasive thermometry and computer simulations for treatment planning

“…Only four of the reported studies in Table 3 have already been used for in vivo applications, namely Dennis et al [14] (commercial multicore BNF nanoparticles), Rodrigues [23], with some reporting partial or even complete remissions outcomes in solid murine tumoral models for animals that underwent MNH. In particular, the BNF nanoparticle is probably the most widely tested in vivo [14,169,170] nanocarrier of those listed in Table 3, although conclusions from some data should be taken very carefully. For instance, In Dennis et al Ref.…”

Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application

“…Aside from surgical excision, chemotherapy remains the backbone of current breast cancer treatment. However, its clinical use is limited by numerous drawbacks, which require novel therapies based on various combinations of anticancer drugs and procedures [30]. GemOx is a promising treatment strategy in breast cancer treatment because of its non-cross-resistance, synergistic antitumor activity, and tolerability of both drugs.…”