title: Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.
abstract: Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Nathanael A
authors.initials: NA
authors.lastname: Stocke
authors.affiliation: Department of Pharmaceutical Science, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Sethi
authors.affiliation: Department of Pharmaceutical Science, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Amar
authors.initials: A
authors.lastname: Jyoti
authors.affiliation: Department of Pharmaceutical Science, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Chan
authors.affiliation: College of Medicine, Department of Internal Medicine, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Arnold
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: J Zach
authors.initials: JZ
authors.lastname: Hilt
authors.affiliation: Department of Pharmaceutical Science, University of Kentucky, Lexington, KY 40506, USA. Electronic address: m.upreti@uky.edu.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Upreti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D006979:Hyperthermia, Induced / Q000379:methods*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D055909:Magnetic Field Therapy / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000627:therapeutic use*; D051379:Mice; D061206:Neoplasm Micrometastasis / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000473:pathology* / Q000628:therapy
chemical_list: D058185:Magnetite Nanoparticles
keywords: Alternating magnetic field (AMF); Magnetic nanoparticles (MNP); Metastasis and Transmission electron microscopy (TEM); Triple negative breast cancer (TNBC); Tumor tissue analogs (TTA)