Controlled Synthesis and Characterization of Micrometric Single Crystalline Magnetite With Superparamagnetic Behavior and Cytocompatibility/Cytotoxicity Assessments

Claudia Geanina Farcas,Virgil Rotaru,Iulia Pinzaru,Dorina Coricovac,Aurel Ercuta,Marius Constantin Chirita Mihaila,Marius Chirita,Ioana Macasoi,Adrian Ieta,Cristina Dehelean,Liviu Mocanu,Stefana Avram,Felicia Loghin

doi:10.3389/fphar.2020.00410

Abstract

A new class of magnetite (Fe3O4) particles, coined as “Single Crystalline Micrometric Iron Oxide Particles” (SCMIOPs), were obtained by hydrothermal synthesis. Both the single Fe3O4 phase content and the particle sizes range, from 1 µm to 30 µm, can be controlled by synthesis. The notable finding states that these particles exhibit vanishing remanent magnetization (σr=0.28 emu/g) and coercive force (Hc=1.5 Oe), which indicate a superparamagnetic-like behavior (unexpected at micrometric particles size), and remarkably high saturation magnetization (σs=95.5 emu/g), what ensures strong magnetic response, and the lack of agglomeration after the magnetic field removal. These qualities make such particles candidates for biomedical applications, to be used instead of magnetic nanoparticles which inevitably involve some drawbacks like aglommeration and insufficient magnetic response. In this sense, cytocompatibility/cytotoxicity tests were performed on human cells, and the results have clearly indicated that SCMIOPs are cytocompatible for healthy cell lines HaCaT (human keratinocytes) and HEMa (primary epidermal melanocytes) and cytotoxic for neoplastic cell lines A375 (human melanoma) and B164A5 (murine melanoma) in a dose-dependent manner.

Highlights

IntroductionIron oxides manufactured as nanoparticles or microparticles are considered materials with multi-purpose biomedical potential that proved great results in different biomedical applications, as: drugdelivery carriers, cancer therapy (targeted therapy by applying an external magnetic field), hyperthermia, diagnostic agents (nuclear magnetic resonance – NMR, magnetic resonance imaging - MRI), tools for in vitro techniques (diagnostic separation, magnetorelaxometry), etc (Catalano, 2017)
Iron oxides manufactured as nanoparticles or microparticles are considered materials with multi-purpose biomedical potential that proved great results in different biomedical applications, as: drugdelivery carriers, cancer therapy, hyperthermia, diagnostic agents, tools for in vitro techniques, etc (Catalano, 2017)
The results indicate that the 24 h direct contact of SCMIOPs with HaCaT cells led to a decrease of cell viability in a dose-dependent manner

Summary

Introduction

Iron oxides manufactured as nanoparticles or microparticles are considered materials with multi-purpose biomedical potential that proved great results in different biomedical applications, as: drugdelivery carriers, cancer therapy (targeted therapy by applying an external magnetic field), hyperthermia, diagnostic agents (nuclear magnetic resonance – NMR, magnetic resonance imaging - MRI), tools for in vitro techniques (diagnostic separation, magnetorelaxometry), etc (Catalano, 2017). By applying different methods of synthesis were obtained iron oxide microparticles with enhanced biological properties: agglomerations of magnetite nanoparticles with a superparamagnetic core (11.8 μm) and amoxicillin cover for the treatment of the spiral form of gram-negative bacteria Helicobacter pylori (Silva et al, 2009); MIOPs in the range of 1 μm—as contrast agents in mouse brain inflammatory pathology which enabled in vivo detection of the disease; larger MIOPs for cellular MRI imaging (Wu et al, 2006), characterization of vascular inflammatory disease (McAteer et al, 2008; Ye et al, 2008), molecular imaging of thrombosis (Von Zur Muhlen et al, 2009), molecular imaging of tissue ischemia (Akhtar et al, 2010) and as contrast agents for the detection of endovascular molecular targets by MRI (McAteer et al, 2011); magnetic oxide particle suspension in distilled water (10.82 mm average size) as MRI contrast agents (Mathieu and Martel, 2006). It was reported that for molecular magnetic resonance imaging (mMRI), microparticles of iron oxide (MIOPs) create potent hypo intense contrast effects, especially due to their physical size (Mankia et al, 2011)

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