Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism.
Alexey V Yaremenko, Ivan V Zelepukin, Ilya N Ivanov, Roman O Melikov, Nadezhda A Pechnikova, Dzhuliia Sh Dzhalilova, Aziz B Mirkasymov, Vera A Bragina, Maxim P Nikitin, Sergey M Deyev, Petr I Nikitin
Author Information
Alexey V Yaremenko: Center for Nanomedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. aleksei.iaremenko@fulbrightmail.org.
Ivan V Zelepukin: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia.
Ilya N Ivanov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia.
Roman O Melikov: Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, 119991, Moscow, Russia.
Nadezhda A Pechnikova: Saint Petersburg State University, 199034, Saint Petersburg, Russia.
Dzhuliia Sh Dzhalilova: Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution, Petrovsky National Research Centre of Surgery, 117418, Moscow, Russia.
Aziz B Mirkasymov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia.
Vera A Bragina: Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991, Moscow, Russia.
Maxim P Nikitin: Sirius University of Science and Technology, 354340, Sirius, Russia.
Sergey M Deyev: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia.
Petr I Nikitin: National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409, Moscow, Russia. nikitin@kapella.gpi.ru.
Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design.
