Honors & Awards

  • NIH K99/R00 Pathway to Independence Award, National Cancer Institute (NCI) (2020-2026)
  • Marie-Curie Minded Fellowship, Marie Skłodowska-Curie (MSC) COFUND Action Funded by European Union’s Horizon 2020 (2018-2019)
  • NIH T32 Postdoctoral Fellowship, Stanford Cancer Imaging Training (SCIT), Stanford University (2016-2018)
  • World Molecular Imaging Congress (WMIC) Travel Award, Magnetic Insight Inc. (2017)
  • Distinguished Young Scholar Award, University of Washington (2016)
  • Materials Research Society (MRS) Graduate Students Award, Materials Research Society (MRS) (2016)
  • Super-resolution Fluorescent Microscopy Workshop scholarship, University of Washington (2015)
  • Graduate School Conference Travel Award, University of Washington (2014)
  • Advanced Future Faculty workshop & Materials Genome Initiative travel award, Northeastern University, National Science Foundation (NSF) (2013)

Education & Certifications

  • PhD (Dual title), University of Washington, Materials Science and Engineering & Nanotechnology and Molecular Engineering (2015)
  • MS, Sharif University of Technology, Materials Science and Engineering (2008)
  • BS, Sharif University of Technology, Materials Science and Engineering (2005)

All Publications

  • Intraoperative Assessment and Photothermal Ablation of the Tumor Margins Using Gold Nanoparticles Advanced Science Wei*, Q., (* co-first author) Arami* , H., Santos*, H. A., Zhang*, H., Li*, Y., He, J., Zhong, D., Ling, D., Zhou, M. 2021
  • Simultaneous Deep Tracking of Stem Cells by Surface Enhanced Raman Imaging Combined with Single‐Cell Tracking by NIR‐II Imaging in Myocardial Infarction Advanced Functional Materials Hua*, S., Zhong*, S., (* co-first author) Arami*, H., He*, J., Zhong, D., Zhang, D., Chen, X., Qian, J., Hu, X., Zhou, M. 2021; 31: 1-14

    View details for DOI 10.1002/adfm.202100468

  • Magneto-plasmonic nanostars for image-guided and NIR-triggered drug delivery SCIENTIFIC REPORTS Tomitaka, A., Arami, H., Ahmadivand, A., Pala, N., McGoron, A. J., Takemura, Y., Febo, M., Nair, M. 2020; 10 (1): 10115


    Smart multifunctional nanoparticles with magnetic and plasmonic properties assembled on a single nanoplatform are promising for various biomedical applications. Owing to their expanding imaging and therapeutic capabilities in response to external stimuli, they have been explored for on-demand drug delivery, image-guided drug delivery, and simultaneous diagnostic and therapeutic (i.e. theranostic) applications. In this study, we engineered nanoparticles with unique morphology consisting of a superparamagnetic iron oxide core and star-shaped plasmonic shell with high-aspect-ratio gold branches. Strong magnetic and near-infrared (NIR)-responsive plasmonic properties of the engineered nanostars enabled multimodal quantitative imaging combining advantageous functions of magnetic resonance imaging (MRI), magnetic particle imaging (MPI), photoacoustic imaging (PAI), and image-guided drug delivery with a tunable drug release capacity. The model drug molecules bound to the core-shell nanostars were released upon NIR illumination due to the heat generation from the core-shell nanostars. Moreover, our simulation analysis showed that the specific design of the core-shell nanostars demonstrated a pronounced multipolar plasmon resonance, which has not been observed in previous reports. The multimodal imaging and NIR-triggered drug release capabilities of the proposed nanoplatform verify their potential for precise and controllable drug release with different applications in personalized medicine.

    View details for DOI 10.1038/s41598-020-66706-2

    View details for Web of Science ID 000543969500016

    View details for PubMedID 32572041

    View details for PubMedCentralID PMC7308341

  • Hollow Micro and Nanostructures for Therapeutic and Imaging Applications Journal of Drug Delivery Science and Technology Yasun, E., Gandhi, S., Choudhury, S., Mohammadinejad, R., Benyettou, F., Gozubenli, N., Arami, H. 2020
  • The CpG Molecular Structure Controls Mineralization of Calcium Phosphate Nanoparticles and their Immunostimulation Efficacy as Vaccine Adjuvants Nanoscale Khalifehzadeh*, R., (* co-first author) Arami*, H. 2020; 12: 9603-9615
  • Biodegradable calcium phosphate nanoparticles for cancer therapy Advances in Colloid and Interface Science Khalifehzadeh*, R., (* co-first author) Arami* , H. 2020 ; 279: 1-20
  • Plasmonic and electrostatic interactions enable uniformly-enhanced liquid bacterial surface-enhanced Raman scattering (SERS) Nano Letters Tadesse, L. F., Ho, C., Chen, D., Arami, H., Banaei, N., Gambhir, S. S., Jeffrey, S. S., Saleh, A. A., Dionne, J. A. 2020
  • Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial ACS NANO Arami, H., Patel, C. B., Madsen, S. J., Dickinson, P. J., Davis, R. M., Zeng, Y., Sturges, B. K., Woolard, K. D., Habte, F. G., Akin, D., Sinclair, R., Gambhir, S. S. 2019; 13 (3): 2858–69
  • DNA-templated strontium-doped calcium phosphate nanoparticles for gene delivery in bone cells ACS Biomaterials Science and Engineering Khalifehzadeh, R., Arami, H. 2019; 5 (7): 3201-3211
  • Dynamic magnetic characterization and magnetic particle imaging enhancement of magnetic-gold core-shell nanoparticles NANOSCALE Tomitaka, A., Ota, S., Nishimoto, K., Arami, H., Takemura, Y., Nair , M. 2019; 11 (13): 6489-6496

    View details for DOI 10.1039/C9NR00242A

  • Tumor Treating Fields Increases Membrane Permeability in Glioblastoma Cells Cell Death Discovery Chang, E., Patel, C. B., Pohling, C., Young, C., Song, J., Flores, T., Zeng, Y., Joubert, L. M., Arami, H., Natarajan, A., Sinclair, R., Gambhir, S. S. 2018; 4
  • Hybrid magneto-plasmonic liposomes for multimodal image-guided and brain-targeted HIV treatment NANOSCALE Tomitaka, A., Arami, H., Huang, Z., Raymond, A., Rodriguez, E., Cai, Y., Febo, M., Takemura, Y., Nair, M. 2018; 10: 184-194

    View details for DOI 10.1039/C7NR07255D

  • Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy. Oncotarget Tripathi, P. P., Arami, H. n., Banga, I. n., Gupta, J. n., Gandhi, S. n. 2018; 9 (98): 37252–67


    Delivery of imaging reagents and drugs to tumors is essential for cancer diagnosis and therapy. In addition to therapeutic and diagnostic functionalities, peptides have potential benefits such as biocompatibility, ease to synthesize, smaller size, by-passing off-target side effects, and achieving the beneficial effects with lower-administered dosages. A particular type of peptide known as cell penetrating peptides (CPP) have been predominantly studied during last twenty years as they are not only capable to translocate themselves across membranes but also allow carrier drugs to translocate across plasma membrane, by different mechanisms depending on the CPP. This is of great potential importance in drug delivery systems, as the ability to pass across membranes is crucial to many drug delivery systems. In spite of significant progress in design and application of CPP, more investigations are required to further improve their delivery to tumors, with reduced side-effect and enhanced therapeutic efficacy. In this review, we emphasis on current advancements in preclinical and clinical trials based on using CPP for more efficient delivery of anti-cancer drugs and imaging reagents to cancer tissues and individual cells associated with them. We discuss the evolution of the CPPs-based strategies for targeted delivery, their current status and strengths, along with summarizing the role of CPPs in targeted drug delivery. We also discuss some recently reported diagnostic applications of engineered protease-responsive substrates and activable imaging complexes. We highlight the recent clinical trial data by providing a road map for better design of the CPPs for future preclinical and clinical applications.

    View details for PubMedID 30647857

    View details for PubMedCentralID PMC6324683

  • An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nature biomedical engineering Vermesh, O., Aalipour, A., Ge, T. J., Saenz, Y., Guo, Y., Alam, I. S., Park, S., Adelson, C. N., Mitsutake, Y., Vilches-Moure, J., Godoy, E., Bachmann, M., Ooi, C. C., Lyons, J. K., Mueller, K., Arami, H., Green, A., Solomon, E. I., Wang, S. X., Gambhir, S. S. 2018; 2: 696–705


    The detection and analysis of rare blood biomarkers is necessary for early cancer diagnosis and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumor cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 mL of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. We have developed a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labeled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labeling and single-pass capture of viable model CTCs in less than 10 seconds. The wire achieves capture efficiencies that correspond to enrichments of 10-80 times the amount of CTCs in a 5-mL blood draw, and to 500-5,000 times the enrichments achieved by the commercially available Gilupi CellCollector.

    View details for PubMedID 30524876

  • Image-Guided Therapy ADVANCES IN PERSONALIZED NANOTHERAPEUTICS Tomitaka, A., Arami, H., Takemura, Y., Nair, M. 2017: 41-55
  • Development of magneto-plasmonic nanoparticles for multimodal image-guided therapy to the brain NANOSCALE Tomitaka, A., Arami, H., Raymond, A., Yndart, A., Kaushik, A., Jayant, R. D., Takemura, Y., Cai, Y., Toborek, M., Nair, M. 2017; 9 (2): 764-773


    Magneto-plasmonic nanoparticles are one of the emerging multi-functional materials in the field of nanomedicine. Their potential for targeting and multi-modal imaging is highly attractive. In this study, magnetic core/gold shell (MNP@Au) magneto-plasmonic nanoparticles were synthesized by citrate reduction of Au ions on magnetic nanoparticle seeds. Hydrodynamic size and optical properties of magneto-plasmonic nanoparticles synthesized with the variation of Au ions and reducing agent concentrations were evaluated. The synthesized magneto-plasmonic nanoparticles exhibited superparamagnetic properties, and their magnetic properties contributed to the concentration-dependent contrast in magnetic resonance imaging (MRI). The imaging contrast from the gold shell part of the magneto-plasmonic nanoparticles was also confirmed by X-ray computed tomography (CT). The transmigration study of the magneto-plasmonic nanoparticles using an in vitro blood-brain barrier (BBB) model proved enhanced transmigration efficiency without disrupting the integrity of the BBB, and showed potential to be used for brain diseases and neurological disorders.

    View details for DOI 10.1039/c6nr07520gD

    View details for Web of Science ID 000394780200035

    View details for PubMedID 27976764

    View details for PubMedCentralID PMC5325696

  • Tomographic magnetic particle imaging of cancer targeted nanoparticles NANOSCALE Arami, H., Teeman, E., Troksa, A., Bradshaw, H., Saatchi, K., Tomitaka, A., Gambhir, S. S., Häfeli, U. O., Liggitt, D., Krishnan, K. M. 2017; 9: 18723-18730

    View details for DOI 10.1039/C7NR05502A

  • Surface-enhanced Raman Spectroscopy (SERS) For Intraoperative Brain Tumor Imaging And Photothermal Therapy NEURO-ONCOLOGY Arami, H., Chang, E., Patel, C. B., Madsen, S. J., Davis, R. M., Sinclair, R., Gambhir, S. S. 2017; 19: vi159
  • Detection of Cancer-Specific Proteases Using Magnetic Relaxation of Peptide-Conjugated Nanoparticles in Biological Environment NANO LETTERS Gandhi, S., Arami, H., Krishnan, K. M. 2016; 16 (6): 3668-3674


    Protease expression is closely linked to malignant phenotypes of different solid tumors; as such, their detection is promising for diagnosis and treatment of cancers, Alzheimer's, and vascular diseases. Here, we describe a new method for detecting proteases by sensitively monitoring the magnetic relaxation of monodisperse iron oxide nanoparticles (IONPs) using magnetic particle spectrometer (MPS). In this assay, tailored peptides functioning as activatable nanosensors link magnetic nanoparticles and possess selective sites that are recognizeable and cleaveable by specific proteases. When these linker peptides, labeled with biotin at N- and C-terminals, are added to the neutravidin functionalized IONPs, nanoparticles aggregate, resulting in well-defined changes in the MPS signal. However, as designed, in the presence of proteases these peptides are cleaved at predetermined sites, redispersing IONPs, and returning the MPS signal(s) close to its preaggregation state. These changes observed in all aspects of the MPS signal (peak intensity, its position as a function of field amplitude, and full width at half-maximum-when combined, these three also eliminate false positives), help to detect specific proteases, relying only on the magnetic relaxation characteristics of the functionalized nanoparticles. We demonstrate the general utility of this assay by detecting one each from the two general classes of proteases: trypsin (digestive serine protease, involved in various cancers, promoting proliferation, invasion, and metastasis) and matrix metalloproteinase (MMP-2, observed through metastasis and tumor angiogenesis). This MPS based protease-assay is rapid, reproducible, and highly sensitive and can form the basis of a feasible, high-throughput method for detection of various other proteases.

    View details for DOI 10.1021/acs.nanolett.6b00867

    View details for Web of Science ID 000377642700038

    View details for PubMedID 27219521

  • Ferromagnetic FePt/Au Core/Shell Nanoparticles Prepared Via Solvothermal Annealing IEEE MAGNETICS LETTERS Poudyal, N., Gandha, K., Liu, ., Arami , H., Liu , J. 2016
  • Low drive field amplitude for improved image resolution in magnetic particle imaging Medical Physics Croft , L., Goodwill , P., Konkle , J., Arami , H., Price, D., Li , A., Saritas , E., Conolly, S. 2016 ; 43 (424)

    View details for DOI 10.1118/1.4938097

  • Magnetic Particle Imaging (MPI) Tracers for In Vivo Applications Arami , H. 2016
  • In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents BIOMATERIALS Arami, H., Khandhar, A. P., Tomitaka, A., Yu, E., Goodwill, P. W., Conolly, S. M., Krishnan, K. M. 2015; 52: 251-261


    Magnetic Particle Imaging (MPI) is a novel non-invasive biomedical imaging modality that uses safe magnetite nanoparticles as tracers. Controlled synthesis of iron oxide nanoparticles (NPs) with tuned size-dependent magnetic relaxation properties is critical for the development of MPI. Additional functionalization of these NPs for other imaging modalities (e.g. MRI and fluorescent imaging) would accelerate screening of the MPI tracers based on their in vitro and in vivo performance in pre-clinical trials. Here, we conjugated two different types of poly-ethylene-glycols (NH2-PEG-NH2 and NH2-PEG-FMOC) to monodisperse carboxylated 19.7 nm NPs by amide bonding. Further, we labeled these NPs with Cy5.5 near infra-red fluorescent (NIRF) molecules. Bi-functional PEG (NH2-PEG-NH2) resulted in larger hydrodynamic size (∼98 nm vs. ∼43 nm) of the tracers, due to inter-particle crosslinking. Formation of such clusters impacted the multimodal imaging performance and pharmacokinetics of these tracers. We found that MPI signal intensity of the tracers in blood depends on their plasmatic clearance pharmacokinetics. Whole body mice MPI/MRI/NIRF, used to study the biodistribution of the injected NPs, showed primary distribution in liver and spleen. Biodistribution of tracers and their clearance pathway was further confirmed by MPI and NIRF signals from the excised organs where the Cy5.5 labeling enabled detailed anatomical mapping of the tracers.in tissue sections. These multimodal MPI tracers, combining the strengths of each imaging modality (e.g. resolution, tracer sensitivity and clinical use feasibility) pave the way for various in vitro and in vivo MPI applications.

    View details for DOI 10.1016/j.biomaterials.2015.02.040

    View details for Web of Science ID 000353091000023

    View details for PubMedID 25818431

  • Magnetic Particle Imaging With Tailored Iron Oxide Nanoparticle Tracers IEEE TRANSACTIONS ON MEDICAL IMAGING Ferguson, R. M., Khandhar, A. P., Kemp, S. J., Arami, H., Saritas, E. U., Croft, L. R., Konkle, J., Goodwill, P. W., Halkola, A., Rahmer, J., Borgert, J., Conolly, S. M., Krishnan, K. M. 2015; 34 (5): 1077-1084


    Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2(∗) -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

    View details for DOI 10.1109/TMI.2014.2375065

    View details for Web of Science ID 000353899600006

    View details for PubMedID 25438306

  • Tuning Surface Coatings of Optimized Magnetite Nanoparticle Tracers for In Vivo Magnetic Particle Imaging IEEE TRANSACTIONS ON MAGNETICS Khandhar, A. P., Ferguson, R. M., Arami, H., Kemp, S. J., Krishnan, K. M. 2015; 51 (2)
  • Synthesis of phase-pure and monodisperse iron oxide nanoparticles by thermal decomposition NANOSCALE Hufschmid, R., Arami, H., Ferguson, R. M., Gonzales, M., Teeman, E., Brush, L. N., Browning, N. D., Krishnan, K. M. 2015; 7 (25): 11142-11154


    Superparamagnetic iron oxide nanoparticles (SPIONs) are used for a wide range of biomedical applications requiring precise control over their physical and magnetic properties, which are dependent on their size and crystallographic phase. Here we present a comprehensive template for the design and synthesis of iron oxide nanoparticles with control over size, size distribution, phase, and resulting magnetic properties. We investigate critical parameters for synthesis of monodisperse SPIONs by organic thermal decomposition. Three different, commonly used, iron containing precursors (iron oleate, iron pentacarbonyl, and iron oxyhydroxide) are evaluated under a variety of synthetic conditions. We compare the suitability of these three kinetically controlled synthesis protocols, which have in common the use of iron oleate as a starting precursor or reaction intermediate, for producing nanoparticles with specific size and magnetic properties. Monodisperse particles were produced over a tunable range of sizes from approximately 2-30 nm. Reaction parameters such as precursor concentration, addition of surfactant, temperature, ramp rate, and time were adjusted to kinetically control size and size-distribution, phase, and magnetic properties. In particular, large quantities of excess surfactant (up to 25 : 1 molar ratio) alter reaction kinetics and result in larger particles with uniform size; however, there is often a trade-off between large particles and a narrow size distribution. Iron oxide phase, in addition to nanoparticle size and shape, is critical for establishing magnetic properties such as differential susceptibility (dm/dH) and anisotropy. As an example, we show the importance of obtaining the required size and iron oxide phase for application to Magnetic Particle Imaging (MPI), and describe how phase purity can be controlled. These results provide much of the information necessary to determine which iron oxide synthesis protocol is best suited to a particular application.

    View details for DOI 10.1039/c5nr01651g

    View details for Web of Science ID 000356515900035

    View details for PubMedID 26059262

  • Ex Situ and In Situ (S)TEM of Iron Oxide Nanoparticles Synthesized by Decomposition of an Organometallic Precursor MICROSCOPY AND MICROANALYSIS Hufschmid, R., Arami , H., Krishnan, K., Browning , N. 2015 ; 21 (S3): 965-966
  • Quantitative “Hot-Spot” Imaging of Transplanted Stem Cells Using Superparamagnetic Tracers and Magnetic Particle Imaging TOMOGRAPHY Bulte, J., Walczak, P., Janowski, M., Krishnan , K., Arami , H., Halkola, A., Gleich , B., Rahmer , J. 2015; 1 (2): 91-97
  • In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles Chemical Society Reviews Arami , H., Khandhar , A., Liggitt, D., Krishnan , K. 2015 ; 44: 8576-8607

    View details for DOI 10.1039/C5CS00541H

  • Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging NANOSCALE Tomitaka, A., Arami, H., Gandhi, S., Krishnan, K. M. 2015; 7 (40): 16890-16898


    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

    View details for DOI 10.1039/c5nr02831k

    View details for Web of Science ID 000362662100043

    View details for PubMedID 26412614

  • Room-temperature detection of a single 19 nm super-paramagnetic nanoparticle with an imaging magnetometer APPLIED PHYSICS LETTERS Gould, M., Barbour, R. J., Thomas, N., Arami, H., Krishnan, K. M., Fu, K. C. 2014; 105 (7)

    View details for DOI 10.1063/1.4893602

    View details for Web of Science ID 000341189800049

  • Self-consistent magnetic properties of magnetite tracers optimized for magnetic particle imaging measured by ac susceptometry, magnetorelaxometry and magnetic particle spectroscopy JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS Ludwig, F., Remmer, H., Kuhlmann, C., Wawrzik, T., Arami, H., Ferguson, R. M., Krishnan, K. M. 2014; 360: 169-173
  • Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging JOURNAL OF APPLIED PHYSICS Arami, H., Krishnan, K. M. 2014; 115 (17)

    View details for DOI 10.1063/1.4867756

    View details for Web of Science ID 000335643700192

  • Tailoring the magnetic and pharmacokinetic properties of iron oxide magnetic particle imaging tracers BIOMEDICAL ENGINEERING-BIOMEDIZINISCHE TECHNIK Ferguson, R. M., Khandhar, A. P., Arami, H., Hua, L., Hovorka, O., Krishnan, K. M. 2013; 58 (6): 493-507


    Magnetic particle imaging (MPI) is an attractive new modality for imaging distributions of iron oxide nanoparticle tracers in vivo. With exceptional contrast, high sensitivity, and good spatial resolution, MPI shows promise for clinical imaging in angiography and oncology. Critically, MPI requires high-quality iron oxide nanoparticle tracers with tailored magnetic and surface properties to achieve its full potential. In this review, we discuss optimizing iron oxide nanoparticles' physical, magnetic, and pharmacokinetic properties for MPI, highlighting results from our recent work in which we demonstrated tailored, biocompatible iron oxide nanoparticle tracers that provided two times better linear spatial resolution and five times better signal-to-noise ratio than Resovist.

    View details for DOI 10.1515/bmt-2012-0058

    View details for Web of Science ID 000330222800002

    View details for PubMedID 23787461

  • Size-dependent ferrohydrodynamic relaxometry of magnetic particle imaging tracers in different environments MEDICAL PHYSICS Arami, H., Ferguson, R. M., Khandhar, A. P., Krishnan, K. M. 2013; 40 (7)


    Magnetic particle imaging (MPI) is a recently developed imaging technique that seeks to provide ultrahigh resolution and tracer sensitivity with positive contrast directly originated from superparamagnetic iron oxide nanoparticles (NPs). MPI signals can be generated from a combination of Néel relaxation, Brownian rotational diffusion, and hysteretic reversal mechanisms of NPs in response to applied magnetic fields. When specific targeting of organs, such as carcinoma and endothelial cardiovascular cells, is needed, different behavior may be expected in immobilized NPs, due to complete or partial elimination of the Brownian motion. Here, the authors present an experimental investigation of the MPI spatial resolution and signal intensities as a function of a wide range of median core sizes of NPs under four representative conditions, including after immobilization in a tissue equivalent medium.Monodisperse hydrophobic NPs with median core diameters (d0) ranging from 7 to 22 nm were synthesized in organic media and subsequently dispersed in aqueous solution after a facile surface modification. Morphology, median size, size distribution, and magnetic properties of the NPs were investigated. Hydrophobic and hydrophilic NPs with various core sizes were immobilized in trioctyl phosphine oxide and agarose gel, respectively. Their size-dependent performance as MPI tracers for system matrix and x-space image reconstruction was evaluated using magnetic particle spectrometry (MPS) and compared with the free rotating counterparts.Immobilized NPs with core diameters smaller than ≈ 20 nm have similar spatial resolution, but lower signal intensities when compared with their free rotating counterparts. Compared to their performance in solution, spatial resolution was improved, but signal intensity was lower, when larger NPs with core size of 22 nm were immobilized in agarose. Same trends were observed in signal intensities, when considering either system matrix or x-space approaches. The harmonic and dm/dH signal intensities changed linearly and the spatial resolution did not change with decreasing NP concentration up to 15 μg/ml.The results show that the MPI signal is very sensitive to both NP size and environment. The authors' calculations show that Brownian rotational diffusion is slower than the field switching cycle and, therefore, it has minimal influence on MPS signals. dm/dH analyses show that Néel relaxation is the dominant mechanism determining MPI response in smaller NPs (d0 < ≈ 20 nm). Larger NPs show hysteretic reversal when the applied field amplitude is large enough to overcome the coercivity. Linear variation of the MPS signal intensity with iron concentration but with uniform spatial resolution enables quantitative imaging for a range of applications, from high-concentration bolus chase imaging to low-concentration molecular imaging (while the authors' instrument is noise-limited to ≈ millimolar iron concentrations, nanomolar sensitivity is expected for MPI, theoretically). These results pave the way for future application of the authors' synthesized tracers for immobilized or in vivo targeted MPI of tissues.

    View details for DOI 10.1118/1.4810962

    View details for Web of Science ID 000321272200041

    View details for PubMedID 23822441

  • Highly Stable Amine Functionalized Iron Oxide Nanoparticles Designed for Magnetic Particle Imaging (MPI) IEEE TRANSACTIONS ON MAGNETICS Arami, H., Krishnan, K. M. 2013; 49 (7): 3500-3503
  • Targeted Cell Uptake of a Noninternalizing Antibody Through Conjugation to Iron Oxide Nanoparticles in Primary Central Nervous System Lymphoma WORLD NEUROSURGERY Wang, T., Kievit, F. M., Veiseh, O., Arami, H., Stephen, Z. R., Fang, C., Liu, Y., Ellenbogen, R. G., Zhang, M. 2013; 80 (1-2): 134-141


    At present there is no standard of care for patients with primary central nervous system lymphoma (PCNSL) because of the difficulty in delivering therapeutically effective doses of drugs to the intracellular site of the target PCNSL. Here we report the use of an iron oxide nanoparticle to promote the internalization of a PCNSL targeting antibody by target cells.Iron oxide nanoparticles coated with a copolymer of chitosan-grafted polyethylene glycol (NPs) were conjugated with an anti-CD20 single-chain variable fragment-streptavidin fusion protein (FP), and optically activated with Oregon Green 488. The ability of NP-FP to target PCNSL cells was assessed using flow cytometry and the ferrozine assay. Cell internalization of NP-FP was examined by confocal fluorescence microscopy.The antibody-conjugated NPs had a near-neutral zeta potential and remained stable in biological media for more than 1 week, which may minimizes nonspecific cell uptake. The diameter of the NPs was about 70 nm, which is in an optimal range for maximizing cell uptake. The selective binding of these NPs was demonstrated with binding to PCNSL cells 3- to 4-fold higher than binding to control cells. Z-stack imaging by confocal microscopy revealed the NPs were internalized by PCNSL cells.The high-degree specific binding and cell uptake of NP-FP in PCNSL suggests this NP formulation can be further developed to improve therapy of PCNSL.

    View details for DOI 10.1016/j.wneu.2013.01.011

    View details for Web of Science ID 000326651100033

    View details for PubMedID 23298674

  • Monodisperse magnetite nanoparticle tracers for in vivo magnetic particle imaging BIOMATERIALS Khandhar, A. P., Ferguson, R. M., Arami, H., Krishnan, K. M. 2013; 34 (15): 3837-3845


    Magnetic Particle Imaging (MPI) is a new biomedical imaging modality that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide (SPIO) nanoparticle tracer distributions. In this study, we synthesized monodisperse tracers for enhanced MPI performance and investigated both, their blood clearance time using a 25 kHz magnetic particle spectrometer (MPS), and biodistribution using a combination of quantitative T2-weighted MRI and tissue histology. In vitro and in vivo MPI performance of our magnetic nanoparticle tracers (MNTs), subject to biological constraints, were compared to commercially available SPIOs (Resovist). Monodisperse MNTs showed a 2-fold greater signal per unit mass, and 20% better spatial resolution. In vitro evaluation of tracers showed that MPI performance of our MNTs is preserved in blood, serum-rich cell-culture medium and gel; thus independent of changes in hydrodynamic volume and fluid viscosity - a critical prerequisite for in vivo MPI. In a rodent model, our MNTs circulated for 15 min - 3× longer than Resovist - and supported our in vitro evaluation that MPI signal is preserved in the physiological environment. Furthermore, MRI and histology analysis showed that MNTs distribute in the reticuloendothelial system (RES) in a manner similar to clinically approved SPIO agents. MNTs demonstrating long-circulation times and optimized MPI performance show potential as angiography tracers and blood-pool agents for the emerging MPI imaging modality.

    View details for DOI 10.1016/j.biomaterials.2013.01.087

    View details for Web of Science ID 000317168700011

    View details for PubMedID 23434348

  • ASSESSING THE LIMITS OF MPI TRACER PERFORMANCE International Workshop on Magnetic Particle Imaging (IWMPI) Ferguson, R. M., Khandhar, A. P., Arami, H., Conolly, S. M., Krishnan, K. M. IEEE. 2013
  • ROLE OF BIOFUNCTIONALIZATION AND TRACER CROSS-LINKING IN MAGNETIC PARTICLE SPECTROMETRY International Workshop on Magnetic Particle Imaging (IWMPI) Arami, H., Ferguson, R. M., Khandhar, A. P., Tomitaka, A., Krishnan, K. M. IEEE. 2013
  • Physical and biological optimization of core-shell nanoparticle tracers for in vivo MPI International Workshop on Magnetic Particle Imaging (IWMPI) Khandhar, A. P., Ferguson, R. M., Arami, H., Krishnan, K. M. IEEE. 2013
  • Targeting of Primary Breast Cancers and Metastases in a Transgenic Mouse Model Using Rationally Designed Multifunctional SPIONs ACS NANO Kievit, F. M., Stephen, Z. R., Veiseh, O., Arami, H., Wang, T., Lai, V. P., Park, J. O., Ellenbogen, R. G., Disis, M. L., Zhang, M. 2012; 6 (3): 2591-2601


    Breast cancer remains one of the most prevalent and lethal malignancies in women. The inability to diagnose small volume metastases early has limited effective treatment of stage 4 breast cancer. Here we report the rational development and use of a multifunctional superparamagnetic iron oxide nanoparticle (SPION) for targeting metastatic breast cancer in a transgenic mouse model and imaging with magnetic resonance (MR). SPIONs coated with a copolymer of chitosan and polyethylene glycol (PEG) were labeled with a fluorescent dye for optical detection and conjugated with a monoclonal antibody against the neu receptor (NP-neu). SPIONs labeled with mouse IgG were used as a nontargeting control (NP-IgG). These SPIONs had desirable physiochemical properties for in vivo applications such as near neutral zeta potential and hydrodynamic size around 40 nm and were highly stable in serum containing medium. Only NP-neu showed high uptake in neu expressing mouse mammary carcinoma (MMC) cells which was reversed by competing free neu antibody, indicating their specificity to the neu antigen. In vivo, NP-neu was able to tag primary breast tumors and significantly, only NP-neu bound to spontaneous liver, lung, and bone marrow metastases in a transgenic mouse model of metastatic breast cancer, highlighting the necessity of targeting for delivery to metastatic disease. The SPIONs provided significant contrast enhancement in MR images of primary breast tumors; thus, they have the potential for MRI detection of micrometastases and provide an excellent platform for further development of an efficient metastatic breast cancer therapy.

    View details for DOI 10.1021/nn205070h

    View details for Web of Science ID 000301945900076

    View details for PubMedID 22324543

  • Cell transcytosing poly-arginine coated magnetic nanovector for safe and effective siRNA delivery BIOMATERIALS Veiseh, O., Kievit, F. M., Mok, H., Ayesh, J., Clark, C., Fang, C., Leung, M., Arami, H., Park, J. O., Zhang, M. 2011; 32 (24): 5717-5725


    Lack of safe and effective carriers for delivery of RNA therapeutics remains a barrier to its broad clinical application. We report the development of a cell tanscytosing magnetic nanovector engineered as an siRNA carrier. Iron oxide nanoparticles were modified with poly(ethylene glycol) (PEG), small interfering RNA (siRNA), and a cationic polymer layer. Three nanovector formulations with cationic polymer coatings of poly-arginine (pArg), polylysine (pLys), and polyethylenimine (PEI), respectively, were prepared. The three nanovector formulations where evaluated for safety and ability to promote gene silencing in three types of cancer cells C6/GFP(+), MCF7/GFP(+), and TC2/GFP(+), mimicking human cancers of the brain, breast, and prostate, respectively. Cell viability and fluorescence quantification assays revealed that pArg-coated nanovectors were most effective in promoting gene knockdown and least toxic of the three nanovector formulations tested. Transmission electron microscopy (TEM) imaging of nanovector treated cells further demonstrated that pArg-coated nanovectors enter cells through cell transcytosis, while pLys and PEI coated nanovectors enter cells endocytosis. Our findings suggest that NPs engineered to exploit the cell transcytosis intracellular trafficking pathway may offer a more safe and efficient route for siRNA delivery.

    View details for DOI 10.1016/j.biomaterials.2011.04.039

    View details for Web of Science ID 000292431100018

    View details for PubMedID 21570721

  • Chitosan-coated iron oxide nanoparticles for molecular imaging and drug delivery Advances in Polymer Science Arami , H., Stephen , Z., Veiseh , O., Zhang , M. 2011; 243: 163-184

    View details for DOI 10.1007/12_2011_121

  • Synthesis and Characterization of Magnetic FePt/Au Core/Shell Nanoparticles JOURNAL OF PHYSICAL CHEMISTRY C Yano, K., Nandwana, V., Chaubey, G. S., Poudyal, N., Kang, S., Arami, H., Griffis, J., Liu, J. P. 2009; 113 (30): 13088-13091

    View details for DOI 10.1021/jp901985u

    View details for Web of Science ID 000268233800028

  • Rapid formation of hydroxyapatite nanostrips via microwave irradiation JOURNAL OF ALLOYS AND COMPOUNDS Arami, H., Mohajerani, M., Mazloumi, M., Khalifehzadeh, R., Lak, A., Sadrnezhaad, S. K. 2009; 469 (1-2): 391-394
  • Self-assembled nanostructured ZnO hollow spheres with UVA luminescence ADVANCES IN APPLIED CERAMICS Arami, H., Mazloumi, M., Khalifehzadeh, R., Sadrnezhaad, S. K. 2009; 108 (2): 73-77
  • Self-assembly of ZnO nanoparticles and subsequent formation of hollow microspheres JOURNAL OF ALLOYS AND COMPOUNDS Mazloumi, M., Taghavi, S., Arami, H., Zanganeh, S., Kajbafvala, A., Shayegh, M. R., Sadrnezhaad, S. K. 2009; 468 (1-2): 303-307
  • Effect of predeformation and heat treatment conditions in the SIMA process on microstructural and mechanical properties of A319 aluminum alloy JOURNAL OF ALLOYS AND COMPOUNDS Arami, H., Khalifehzadeh, R., Keyvan, H., Khomamizadeh, F. 2009; 468 (1-2): 130-135
  • Synthesis of γ-Alumina Nanopowders from Synthetic Bayer Liquor and its Application for Oil and Gas Industries JOURNAL OF NANOCOMPOSITE MATERIALS RESEARCH (JNMR) Sadrnezhaad , S., Mazloumi , M., Arami , H., Khalifehzadeh , R. 2009 ; 1 (2): 71-76
  • Rapid Formation of Mono-Dispersed Hydroxyapatite Nanorods with Narrow-Size Distribution via Microwave Irradiation JOURNAL OF THE AMERICAN CERAMIC SOCIETY Lak, A., Mazloumi, M., Mohajerani, M. S., Zanganeh, S., Shayegh, M. R., Kajbafvala, A., Arami, H., Sadrnezhaad, S. K. 2008; 91 (11): 3580-3584
  • Surfactant free hydrothermal formation of Pb3O4 nanorods JOURNAL OF ALLOYS AND COMPOUNDS Arami, H., Mazloumi, M., Khalifehzadeh, R., Sadrnezhaad, S. K. 2008; 466 (1-2): 323-325
  • Mechanical induced reaction in Al-CuO system for in-situ fabrication of Al based nanocomposites JOURNAL OF ALLOYS AND COMPOUNDS Arami, H., Simchi, A., Reihani, S. M. 2008; 465 (1-2): 151-156
  • Self-Assembly of Dandelion-Like Hydroxyapatite Nanostructures Via Hydrothermal Method JOURNAL OF THE AMERICAN CERAMIC SOCIETY Lak, A., Mazloumi, M., Mohajerani, M., Kajbafvala, A., Zanganeh, S., Arami, H., Sadrnezhaad, S. K. 2008; 91 (10): 3292-3297
  • Bundles of self-assembled boehmite nanostrips from a surfactant free hydrothermal route JOURNAL OF ALLOYS AND COMPOUNDS Arami, H., Mazloumi, M., Khalifehzadeh, R., Sadrnezhaad, S. K. 2008; 461 (1-2): 551-554
  • Microporosity control and thermal-fatigue resistance of A319 aluminum foundry alloy MATERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROSTRUCTURE AND PROCESSING Arami, H., Khalifetizadeh, R., Akbari, M., Khomamizadeh, F. 2008; 472 (1-2): 107-114
  • Self-assembled dahlia-like cadmium hydrogen phosphate hydrate nanostructures as templates for cadmium hydroxyapatite hexagonal prisms JOURNAL OF CRYSTAL GROWTH Arami, H., Mazloumi, M., Khalifehzadeh, R., Lak, A., Sadrnezhaad, S. K. 2007; 309 (1): 37-42
  • Interfacial energy determination of nano-scale precipitates by CALPHAD description of Gibbs-Thomson effect JOURNAL OF MATERIALS SCIENCE Shahandeh, S., Arami, H., Sadrnezhaad, S. K. 2007; 42 (22): 9440-9446
  • Electron beam-induced "nanocalcination" of boehmite nanostrips to mesoporous alpha-alumina phase JOURNAL OF THE AMERICAN CERAMIC SOCIETY Arami, H., Mazloumi, M., Khalifehzadeh, R., Khatiboleslam, S., Sadrnezhaadw, S. K. 2007; 90 (10): 3311-3313
  • Polypyrrole/multiwall carbon nanotube nanocomposites electropolymerized on copper substrate MATERIALS LETTERS Arami, H., Mazloumi, M., Khalifehzadeh, R., Emami, S. H., Sadrnezhaad, S. K. 2007; 61 (22): 4412-4415
  • Prediction of the effect of vacuum sintering conditions on porosity and hardness of porous NiTi shape memory alloy using ANFIS COMPUTATIONAL MATERIALS SCIENCE Khalifehzadeh, R., Forouzan, S., Arami, H., Sadrnezhaad, S. K. 2007; 40 (3): 359-365
  • Sonochemical preparation of TiO2 nanoparticles MATERIALS LETTERS Arami, H., Mazloumi, M., Khalifehzadeh, R., Sadmezhaad, S. K. 2007; 61 (23-24): 4559-4561
  • Reactive milling synthesis of nanocrystalline Al-Cu/Al2O3 nanocomposite MATERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROSTRUCTURE AND PROCESSING Arami, H., Simchi, A. 2007; 464 (1-2): 225-232
  • Studies on synthesis of alumina nanopowder from synthetic Bayer liquor MATERIALS RESEARCH BULLETIN Mazloumi, M., Arami, H., Khalifehzadeh, R., Sadrnezhaad, S. K. 2007; 42 (6): 1004-1009
  • Alumina nanopowder production from synthetic Bayer liquor JOURNAL OF THE AMERICAN CERAMIC SOCIETY Mazloumi, M., Khalifehzadeh, R., Sadrnezhaad, S. K., Arami, H. 2006; 89 (12): 3654-3657
  • Flower-like bundles of ZnO nanosheets as an intermediate between hollow nanosphere and nanoparticles MATERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROSTRUCTURE AND PROCESSING Eftekhari, A., Molaei, F., Arami, H. 2006; 437 (2): 446-450
  • Powder metallurgical fabrication and characterization of nanostructured porous NiTi shape-memory alloy MATERIALS AND MANUFACTURING PROCESSES Sadrnezhaad, S. K., Arami, H., Keivan, H., Khalifezadeh, R. 2006; 21 (8): 727-735