Heparin-coated iron oxide nanoparticles: application as a liver contrast agent, toxicity and pharmacokinetics

Anna Fakhardo; Elizaveta Anastasova; Victor Makarov; Evgeniia Ikonnikova; Ekaterina Kulko; Nikol Agadzhanian; Marina Yakunina; Liubov Shkodenko; Sofia Tsvetikova; Maria Toropko; Elena Koshel; Mikhail Zakharov; Georgii Alexandrov; Olga Khuttunen; Pavel Kulikov; Oleg Burmistrov; Vladimir Vinogradov; Artur Prilepskii

doi:10.1039/D2TB00759B

Heparin-coated iron oxide nanoparticles: application as a liver contrast agent, toxicity and pharmacokinetics†

Anna Fakhardo,

*^ab Elizaveta Anastasova,^a Victor Makarov,^c Evgeniia Ikonnikova,^a Ekaterina Kulko,^a Nikol Agadzhanian,^a Marina Yakunina,^d Liubov Shkodenko,^a Sofia Tsvetikova,^a Maria Toropko,^a Elena Koshel,^a Mikhail Zakharov,^e Georgii Alexandrov,^e Olga Khuttunen,^e Pavel Kulikov,^f Oleg Burmistrov,

^g Vladimir Vinogradov^a and Artur Prilepskii^a

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* Corresponding authors

^a International Institute “Solution Chemistry of Advanced Materials and Technology”, ITMO University, Lomonosova, 9 Saint-Petersburg 197101, Russian Federation
E-mail: affakhardo@gmail.com

^b College of Medicine,Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA

^c Granov Russian Research Center of Radiology & Surgical Technologies, 70 Leningradskaya Street, Pesochny, Saint-Petersburg 197758, Russian Federation

^d Blokhin National Medical Research Center of Oncology, Kashirskoe highway, 23 Moscow 115478, Russian Federation

^e Pharmacogen Ltd, Veterans avenue, 26, A, St. Petersburg 198215, Russian Federation

^f Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, Pogodinskaya street, 10, 1 Moscow, Russian Federation

^g School of Physics and Engineering, ITMO University, Saint Petersburg, Russian Federation

Abstract

The prepared heparin-coated iron oxide nanoparticles (Hep-IONPs) contrasted cholangioma tumors in the liver in T₂ MRI. The NPs were not toxic to rats and rabbits after 14 days of consecutive IV injections as observed from the monitoring of the body weight and biochemical and hematological parameters. No embryotoxic or immunotoxic side effects of the material were detected. However, we observed mutagenicity of iron oxide NPs in the Ames test and micronucleus assay. The pharmacokinetic studies showed that Hep-IONPs circulated in the blood for 14 days after IV injection. The liver iron level reached its maximum after 6 hours and slowly decreased within 30 days. Altogether, these results suggest that the synthesized Hep-IONPs are promising for use as the MRI contrast agent to identify liver malignancies.

Journal of Materials Chemistry B

Heparin-coated iron oxide nanoparticles: application as a liver contrast agent, toxicity and pharmacokinetics†

Abstract

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Heparin-coated iron oxide nanoparticles: application as a liver contrast agent, toxicity and pharmacokinetics

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