Biodistribution and targeting properties of iron oxide nanoparticles for treatments of cancer and iron anemia disease

Abstract

IONP (iron oxide nanoparticles) commercialized for treatments of iron anemia or cancer diseases can be administered at doses exceeding 1 g per patient, indicating their bio-compatibility when they are prepared in the right conditions. Various parameters influence IONP biodistribution such as nanoparticle size, hydrophobicity/hydrophilicity, surface charge, core composition, coating properties, route of administration, quantity administered, and opsonization. IONP biodistribution trends include their capture by the reticuloendothelial system (RES), accumulation in liver and spleen, leading to nanoparticle degradation by macrophages and liver Kupffer cells, possibly followed by excretion in feces. To result in efficient tumor treatment, IONP need to reach the tumor in a sufficiently large quantity, using: (i) passive targeting, i.e. the extravasation of IONP through the blood vessel irrigating the tumor, (ii) molecular targeting achieved by a ligand bound to IONP specifically recognizing a cell receptor, and (iii) magnetic targeting in which a magnetic field gradient guides IONP towards the tumor. As a whole, targeting efficacy is relatively similar for different targeting, yielding a percentage of injected IONP in the tumor of 5.10⁻⁴% to 3%, 0.1% to 7%, and 5.10⁻³% to 2.6% for passive, molecular, and magnetic targeting, respectively. For the treatment of iron anemia disease, IONP are captured by the RES, and dissolved into free iron, which is then made available for the organism. For the treatment of cancer, IONP either deliver chemotherapeutic drugs to tumors, produce localized heat under the application of an alternating magnetic field or a laser, or activate in a controlled manner a sono-sensitizer following ultrasound treatment.

Keywords:

• Iron oxide nanoparticle
• toxicity
• pharmacokinetic
• biodistribution
• liver toxicity
• kidney toxicity
• iron anemia

Acknowledgments

The author would like to thank the BPI (‘banque publique d’investissement, France’), the region of Paris (‘Paris Région Entreprise, France’), the French Research Tax Credit program (‘crédit d’impôt recherche’), the incubator Paris Biotech Santé, the ANRT (CIFRE 2014/0359, CIFRE 2016/0747, CIFRE 2013/0364, CIFRE 2015/976), the Eurostars programs (Nanoneck-2 E9309 and Nanoglioma E11778), the AIR program (‘aide à l’innovation responsable’) from the region of Paris (A1401025Q), the ANR (‘Agence Nationale de la Recherche’) Méfisto, as well as the Universities Paris 6, Paris 11 and the university of turich. The author also would like to thank the Nomis Foundation and Markus Reinhard for their support.

Disclosure statement

The author has been working with the French startup Nanobacterie.