Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies

Barbara Freis; Maria De Los Angeles Ramirez; Céline Kiefer; Sébastien Harlepp; Cristian Iacovita; Céline Henoumont; Christine Affolter-Zbaraszczuk; Florent Meyer; Damien Mertz; Anne Boos; Mariana Tasso; Sonia Furgiuele; Fabrice Journe; Sven Saussez; Sylvie Bégin-Colin; Sophie Laurent

doi:10.3390/pharmaceutics15041104

Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies

Pharmaceutics. 2023 Mar 30;15(4):1104. doi: 10.3390/pharmaceutics15041104.

Authors

Barbara Freis^{1

2}, Maria De Los Angeles Ramirez¹, Céline Kiefer¹, Sébastien Harlepp³, Cristian Iacovita⁴, Céline Henoumont², Christine Affolter-Zbaraszczuk⁵, Florent Meyer⁵, Damien Mertz¹, Anne Boos⁶, Mariana Tasso⁷, Sonia Furgiuele⁸, Fabrice Journe⁸, Sven Saussez⁸, Sylvie Bégin-Colin¹, Sophie Laurent²

Affiliations

¹ UMR CNRS-UdS 7504, Institut de Physique et Chimie des Matériaux, CNRS, Université de Strasbourg, 23 Rue du Loess, BP 43, 67034 Strasbourg, France.
² Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, UMONS, 19 Avenue Maistriau, 7000 Mons, Belgium.
³ Tumor Biomechanics, INSERM UMR S1109, Institut d'Hématologie et d'Immunologie, 67091 Strasbourg, France.
⁴ Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, 6 Pasteur St., 400349 Cluj-Napoca, Romania.
⁵ Inserm U1121, Centre de Recherche en Biomédecine de Strasbourg, 1 Rue Eugène Boeckel, CS 60026, CEDEX, 67084 Strasbourg, France.
⁶ IPHC UMR 7178, CNRS, Université de Strasbourg, 67000 Strasbourg, France.
⁷ Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET, Diagonal 113 y 64, La Plata 1900, Argentina.
⁸ Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Avenue du Champ de Mars, 8, 7000 Mons, Belgium.

Abstract

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r₂ = 416 s^-1·mM^-1, SAR_MH = 580 W·g^-1, SAR_PTT = 800 W·g^-1; and r₂ = 407 s^-1·mM^-1, SAR_MH = 899 W·g^-1, SAR_PTT = 300 W·g^-1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells.

Keywords: MRI contrast agent; iron oxide nanocubes and nanoplates; magnetic hyperthermia; photothermia; targeting ligand.

Grants and funding

The Region Alsace, France, and the University of Mons are gratefully acknowledged for the doctoral fellowship to Barbara Freis. This project received funding from ANR (EURONANOMED2020-121—THERAGET) under the umbrella of the ERA-NET EuroNanoMed (GA N°723770) of the EU Horizon 2020 Research and Innovation and ProtherWal “Walloon Region via the ProtherWal Society (Agreement 7289)”. SuperBranche is thanked for providing dendron molecules. UMONS acknowledges the financial support of the Fond National de la Recherche Scientifique (FNRS), the ARC Programs of the French Community of Belgium, COST actions and the Walloon region (ProtherWal and Interreg projects). S.F. acknowledges UMONS, EpiCURA Hospital, ProtherWal and the Fund for Medical Research in Hainaut (FRMH).