Biodistribution of antibody-targeted and non-targeted iron oxide nanoparticles in a breast cancer mouse model

Iron oxide nanoparticle (IONP) hyperthermia is a novel therapeutic strategy currently under consideration for the treatment of various cancer types. Systemic delivery of IONP followed by non-invasive activation via a local alternating magnetic field (AMF) results in site-specific energy deposition in the IONP-containing tumor. Targeting IONP to the tumor using an antibody or antibody fragment conjugated to the surface may enhance the intratumoral deposition of IONP and is currently being pursued by many nanoparticle researchers. This strategy, however, is subject to a variety of restrictions in the in vivo environment, where other aspects of IONP design will strongly influence the biodistribution. In these studies, various targeted IONP are compared to non-targeted controls. IONP were injected into BT-474 tumor-bearing NSG mice and tissues harvested 24hrs post-injection. Results indicate no significant difference between the various targeted IONP and the non-targeted controls, suggesting the IONP were prohibitively-sized to incur tumor penetration. Additional strategies are currently being pursued in conjuncture with targeted particles to increase the intratumoral deposition.

[1]  Robert Sinclair,et al.  Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. , 2008, Small.

[2]  Ou Chen,et al.  Fluorescent nanorods and nanospheres for real-time in vivo probing of nanoparticle shape-dependent tumor penetration. , 2011, Angewandte Chemie.

[3]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[4]  R. Perdrisot,et al.  Iron oxide nanoparticles for use as an MRI contrast agent: pharmacokinetics and metabolism. , 1991, Magnetic resonance imaging.

[5]  R. Jain,et al.  Delivering nanomedicine to solid tumors , 2010, Nature Reviews Clinical Oncology.

[6]  D. Leslie-Pelecky,et al.  Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. , 2008, Molecular pharmaceutics.

[7]  Hisataka Kobayashi,et al.  Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores. , 2003, Bioconjugate chemistry.

[8]  Rebekah Drezek,et al.  In vivo biodistribution of nanoparticles. , 2011, Nanomedicine.

[9]  I. Lucet,et al.  Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. , 1996, Journal of microencapsulation.

[10]  Paula M Jacobs,et al.  Preclinical Safety and Pharmacokinetic Profile of Ferumoxtran-10, an Ultrasmall Superparamagnetic Iron Oxide Magnetic Resonance Contrast Agent , 2006, Investigative radiology.

[11]  Scott E McNeil,et al.  Nanoparticle therapeutics: a personal perspective. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[12]  Ja Tate,et al.  Toxicity and biodistribution of activated and non-activated intravenous iron oxide nanoparticles , 2009, BiOS.

[13]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[14]  J C Gore,et al.  Pharmacokinetics of superparamagnetic iron-oxide MR contrast agents in the rat. , 1990, Investigative radiology.

[15]  A. Maitra,et al.  Biodistribution of fluoresceinated dextran using novel nanoparticles evading reticuloendothelial system. , 2000, International journal of pharmaceutics.