Systemically delivered antibody-labeled magnetic iron oxide nanoparticles are less toxic than plain nanoparticles when activated by alternating magnetic fields
Journal
International Journal of Hyperthermia
Journal Volume
37
Journal Issue
3
Pages
59-75
Date Issued
2020
Author(s)
Abstract
Objective: Toxicity from off-target heating with magnetic hyperthermia (MHT) is generally assumed to be understood. MHT research focuses on development of more potent heating magnetic iron oxide nanoparticles (MIONs), yet our understanding of factors that define biodistribution following systemic delivery remains limited. Preclinical development relies on mouse models, thus understanding off-target heating with MHT in mice provides critical knowledge for clinical development. Methods: Eight-week old female nude mice received a single tail vein injection of bionized nanoferrite (BNF) MIONs or a counterpart labeled with a polyclonal human antibody (BNF-IgG) at 1 mg, 3 mg or 5 mg Fe/mouse on day 1. On day 3, mice were exposed to an alternating magnetic field (AMF) having amplitude of 32, 48 or 64 kA/m at ?145 kHz for 20 min. Twenty-four hours later, blood, livers and spleens were harvested and analyzed. Results: Damage to livers was apparent by histology and serum liver enzymes following MHT with BNF or BNF-IgG at doses ?3 mg Fe and AMF amplitudes ?48 kA/m. Differences between effects with BNF vs. BNF-IgG at a dose of 3 mg Fe were noted in all measures, with less damage and increased survival occurring in mice injected with BNF-IgG. Necropsies revealed severe damage to duodenum and upper small intestines, likely the immediate cause of death at the highest MHT doses. Conclusion: Results demonstrate that the MION coating affects biodistribution, which in turn determines off-target effects. Developments to improve heating capabilities of MIONs may be clinically irrelevant without better control of biodistribution. ? 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
Subjects
alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; hemosiderin; immunoglobulin G; iron; lactate dehydrogenase; magnetic nanoparticle; monocrystalline iron oxide nanoparticle; polyclonal antibody; acute toxicity; alanine aminotransferase blood level; alkaline phosphatase blood level; alternating current; alternating magnetic field; animal experiment; animal tissue; antibody labeling; Article; aspartate aminotransferase blood level; autopsy; blood; burn; cause of death; comparative study; controlled study; correlation coefficient; current amplitude; dispersity; duodenum injury; female; histopathology; hydrodynamics; inductively coupled plasma mass spectrometry; injury severity; intestine injury; lactate dehydrogenase blood level; liver function; liver histology; liver injury; liver necrosis; liver tissue; liver toxicity; magnetic field; mouse; nanotoxicology; nonhuman; particle size; skin injury; skin toxicity; spleen injury; spleen tissue; survival; zeta potential
SDGs
Type
journal article