Systemically delivered antibody-labeled magnetic iron oxide nanoparticles are less toxic than plain nanoparticles when activated by alternating magnetic fields

International Journal of Hyperthermia

Sarah E. Beck¹  Preethi Korangath²  Jackie Stewart²  Robert Ivkov²  Chen Hu³  Wei Fu³  Chun-Ting Yang⁴  Feng-Huei Lin⁴  Cordula Grüttner⁵ 

[1] Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine;Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine;Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital;Institute of Biomedical Engineering, National Taiwan University;Micromod Partikeltechnologie GmbH;

关键词: iron oxide nanoparticles;    magnetic nanoparticles;    monoclonal antibody;    alternating magnetic fields;    hyperthermia;   

DOI  :  10.1080/02656736.2020.1776901

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown