Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

[1]  Arutselvan Natarajan,et al.  Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF--induced thermoablative therapy for human breast cancer in mice. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  P Wust,et al.  Clinical hyperthermia of prostate cancer using magnetic nanoparticles: Presentation of a new interstitial technique , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[3]  Anilchandra Attaluri,et al.  New iron-oxide particles for magnetic nanoparticle hyperthermia: an in-vitro and in-vivo pilot study , 2013, Photonics West - Biomedical Optics.

[4]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[5]  A. Curtis,et al.  Surface modified superparamagnetic nanoparticles for drug delivery: Interaction studies with human fibroblasts in culture , 2004, Journal of materials science. Materials in medicine.

[6]  A. J. Tavares,et al.  Analysis of nanoparticle delivery to tumours , 2016 .

[7]  Rocío Costo,et al.  Distribution functions of magnetic nanoparticles determined by a numerical inversion method , 2017 .

[8]  Marie-Isabelle Baraton,et al.  Synthesis, Functionalization and Surface Treatment of Nanoparticles , 2002 .

[9]  S. Ganta,et al.  A review of stimuli-responsive nanocarriers for drug and gene delivery. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[10]  J. A. V. BUTLER,et al.  Theory of the Stability of Lyophobic Colloids , 1948, Nature.

[11]  L. Perlemuter [From theory to practice]. , 1997, Soins. Psychiatrie.

[12]  Jonathan Shannahan,et al.  The biocorona: a challenge for the biomedical application of nanoparticles , 2017, Nanotechnology reviews.

[13]  R. Ivkov,et al.  Evaluation of a PSMA-targeted BNF nanoparticle construct. , 2015, Nanoscale.

[14]  Andris F. Bakuzis,et al.  AC susceptibility as a tool to probe the dipolar interaction in magnetic nanoparticles , 2016, 1604.02978.

[15]  C. Robic,et al.  Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. , 2008, Chemical reviews.

[16]  A. Seifalian,et al.  Magnetic Nanoparticles: New Perspectives in Drug Delivery. , 2017, Current pharmaceutical design.

[17]  Theodore L. DeWeese,et al.  Magnetic nanoparticle heating efficiency reveals magneto-structural differences when characterized with wide ranging and high amplitude alternating magnetic fields , 2011 .

[18]  Kannan M. Krishnan,et al.  Size-Dependent Relaxation Properties of Monodisperse Magnetite Nanoparticles Measured Over Seven Decades of Frequency by AC Susceptometry , 2013, IEEE Transactions on Magnetics.

[19]  G. Gebhart,et al.  Special Report: The 1996 Guide for the Care and Use of Laboratory Animals. , 1997, ILAR journal.

[20]  S. Andò,et al.  Characteristics and biodistribution of cationic liposomes and their DNA complexes. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[21]  Kenneth A. Dawson,et al.  Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts , 2008, Proceedings of the National Academy of Sciences.

[22]  R. Ivkov,et al.  Experimental estimation and analysis of variance of the measured loss power of magnetic nanoparticles , 2017, Scientific Reports.

[23]  R. Ivkov,et al.  Physics of heat generation using magnetic nanoparticles for hyperthermia , 2013, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[24]  C. Köhler Allograft inflammatory factor-1/Ionized calcium-binding adapter molecule 1 is specifically expressed by most subpopulations of macrophages and spermatids in testis , 2007, Cell and Tissue Research.

[25]  Hao Hong,et al.  Molecular imaging and therapy of cancer with radiolabeled nanoparticles. , 2009, Nano today.

[26]  M. Radomski,et al.  Magnetic Nanoparticles in Cancer Theranostics , 2015, Theranostics.

[27]  Lily Yang,et al.  Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer , 2013, International journal of nanomedicine.

[28]  P. L. McCormack,et al.  Ferumoxytol: in iron deficiency anaemia in adults with chronic kidney disease. , 2012, Drugs.

[29]  M. Arciniegas,et al.  Dipolar interaction and demagnetizing effects in magnetic nanoparticle dispersions: Introducing the mean-field interacting superparamagnet model , 2015, 1507.05192.

[30]  R Weissleder,et al.  Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model. , 2000, Radiology.

[31]  Rishi Shanker,et al.  Toxicity of Nanomaterials , 2015, BioMed research international.

[32]  John Crittenden,et al.  Impact of natural organic matter and divalent cations on the stability of aqueous nanoparticles. , 2009, Water research.

[33]  William D Rooney,et al.  Superparamagnetic Iron Oxide Nanoparticles: Diagnostic Magnetic Resonance Imaging and Potential Therapeutic Applications in Neurooncology and Central Nervous System Inflammatory Pathologies, a Review , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  P. J. Hoopes,et al.  The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia. , 2015, Nanomedicine.

[35]  L. Bezdetnaya,et al.  Anticancer Drug Delivery: An Update on Clinically Applied Nanotherapeutics , 2015, Drugs.

[36]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[37]  R. Ivkov,et al.  Internal Magnetic Structure of Nanoparticles Dominates Time‐Dependent Relaxation Processes in a Magnetic Field , 2015 .

[38]  R. Ivkov,et al.  Development of Tumor Targeting Bioprobes (111In-Chimeric L6 Monoclonal Antibody Nanoparticles) for Alternating Magnetic Field Cancer Therapy , 2005, Clinical Cancer Research.

[39]  Daniele Marin,et al.  Emerging applications for ferumoxytol as a contrast agent in MRI , 2015, Journal of magnetic resonance imaging : JMRI.

[40]  J. Kornhuber,et al.  Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system , 2010, Journal of cellular physiology.

[41]  Mohammad Hedayati,et al.  Preliminary study of injury from heating systemically delivered, nontargeted dextran-superparamagnetic iron oxide nanoparticles in mice. , 2012, Nanomedicine.

[42]  Robert Ivkov,et al.  Synthesis and antibody conjugation of magnetic nanoparticles with improved specific power absorption rates for alternating magnetic field cancer therapy , 2007 .

[43]  C. Batich,et al.  Materials Characterization of Feraheme/Ferumoxytol and Preliminary Evaluation of Its Potential for Magnetic Fluid Hyperthermia , 2013, International journal of molecular sciences.

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

[45]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[46]  Christian NDong,et al.  Tumor Cell Targeting by Iron Oxide Nanoparticles Is Dominated by Different Factors In Vitro versus In Vivo , 2015, PloS one.

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

[48]  Y. Qiang,et al.  The effect of particle size distribution on the usage of the ac susceptibility in biosensors , 2006 .

[49]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[50]  B. Derjaguin,et al.  Theory of the stability of strongly charged lyophobic sols and of the adhesion of strongly charged particles in solutions of electrolytes , 1993 .

[51]  Alke Petri-Fink,et al.  Form Follows Function: Nanoparticle Shape and Its Implications for Nanomedicine. , 2017, Chemical reviews.

[52]  R. Ivkov,et al.  Modified Solenoid Coil That Efficiently Produces High Amplitude AC Magnetic Fields With Enhanced Uniformity for Biomedical Applications , 2012, IEEE Transactions on Magnetics.

[53]  Wolfgang Daum,et al.  Application of High Amplitude Alternating Magnetic Fields for Heat Induction of Nanoparticles Localized in Cancer , 2005, Clinical Cancer Research.

[54]  G. Merlo,et al.  Polyethylenimine-based intravenous delivery of transgenes to mouse lung , 1998, Gene Therapy.

[55]  B. Sproat,et al.  Nonviral siRNA delivery to the lung: investigation of PEG-PEI polyplexes and their in vivo performance. , 2009, Molecular pharmaceutics.

[56]  J. Dormann,et al.  Magnetic Relaxation in Fine‐Particle Systems , 2007 .