PEG-Iron Oxide Core-Shell Nanoparticles: In situ Synthesis and In vitro Biocompatibility Evaluation for Potential T 2 -M

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PEG-Iron Oxide Core-Shell Nanoparticles: In situ Synthesis and In vitro Biocompatibility Evaluation for Potential T2-MRI Applications Karina Almeida Barcelos 1 & Marli Luiza Tebaldi 1 & Eryvaldo Socrates Tabosa do Egito 2 & Nádia Miriceia Leão 1 & Daniel Cristian Ferreira Soares 1 Accepted: 29 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Several colloidal nanosystems have been developed aiming biomedical applications that include investigations related to magnetic resonance imaging (MRI) procedures. In this work, a core-shell structure consisting of iron oxide nanoparticles (IONPs) nucleus grafted with polyethylene glycol (PEG)4000 was prepared and evaluated by physicochemical and magnetic characterization. The polymer was covalently immobilized over nanoparticles through a simple and rapid in situ chemical method. The resulting hybrid material was capable of inducing a relevant T2 relaxation time in an average compared to marketed MRI formulations, revealing both physical characteristics and magnetic properties adequate for MRI applications. Furthermore, the in vitro biocompatibility profile was assessed by flow cytometry technique, using healthy human cell lineage (HEK-293). The results indicated good biocompatibility profile and non-anti-proliferative properties, and therefore, IONP-PEG can be considered as a new system candidate as a T2 contrast agent for MRI applications. Keywords T2 MRI contrast agent . In situ synthesis . Core-shell PEG-iron nanoparticles . PEG-IONP biocompatibility profile

1 Introduction Iron oxide nanoparticles (IONPs) have become prevalent in a broad range of research fields due to their unique physicochemical properties, including high surface area and magnetic properties [1]. The magnetite (Fe3O4) and maghemite (γFe2O3) are the crystalline forms that exhibit excellent magnetic properties, good biocompatibility, and low toxicity, even when internally administered for treatment or imaging procedures such as MRI [1–3]. MRI can be classified according to the relaxation process in longitudinal or transverse time-weighted (T1 or T2 contrast, respectively). IONP-based MRI contrast agents are capable of providing images with a high spatial resolution, in both the T1 and T2 imaging, according to the particle size. However, due * Daniel Cristian Ferreira Soares [email protected] 1

Laboratório de Bioengenharia, Universidade Federal de Itajubá campus Itabira, Rua Irma Ivone Drumond, 200, Itabira, Minas Gerais, Brazil

2

Programa de Pós-Graduação em Nanotecnologia Farmacêutica (PPgNANOFARMA), Universidade Federal do Rio Grande do Norte (UFRN), Rua General Gustavo Cordeiro de Faria, S/N, Natal, Rio Grande do Norte, Brazil

to safety concerns, dextran-IONPs were discontinued since cirrhosis cases were related to excess iron-induced oxidative stress; consequently, the development of new T2 formulations is an emerging necessity [4]. Nanoparticles with a diameter lesser than 4 nm are considered good agents for T1 images. On the other hand, particles

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