Magnetic nanoparticles have recently been of interest due to their superparamagnetic properties, biocompatibility, and size, which allows them to be a major candidate for biomedical applications. Iron oxide magnetic nanoparticles modified with heterobifunctional polyethylene oxide ligands have been synthesized to give a background material that offers stability in biological environments.2 Previous research has shown a gain in magnetic properties from creating cluster of nanoparticles.3 Recent work has involved producing a stable crosslink cluster network, which will theoretically have enhanced magnetic and stability properties due to increased size and enhanced anisotropy of the polymer-particle complexes.

This work was supported by the National Science Foundation’s REU program under grant number 1062873, CU COMSET and the School of Materials Science and Engineering.

[1] S. Laurent, S. Dutz, U.O. Hafeli, M. Mahmoudi. Adv Colloid Interfac, 166 (2011) 8-23. [2] S.L. Saville, R.C. Stone, B. Qi, O.T. Meffor. J Mater Chem, 22 (2012) 24909-24917. [3] N. Pothayee, S. Balasubramaniam, N. Pothayee, N. Jain, N. Hu, Y.N.A. Lin, R.M. Davis. Chem B, 1 (2013) 1142-1149. [4] T. Hyeon, S.S. Lee, J. Park, Y. Chung, H. Bin Na. J Am Chem Soc, 123 (2001) 12798-12801. [5] R. Stone, B. Qi, D. Trebatoski, O.T. Mefford. Publication submitted [6] F. Himo, T. Lovell, R. Hilgraf, V.V. Rostovtsev, L. Noodleman, K.B. Sharpless, V.V. Fokin. J Am Chem Soc, 127 (2005) 210-216. [7] J.R. Thomas, X.J. Liu, P.J. Hergenrother. J Am Chem Soc, 127 (2005) 12434-12435. [8] S.S. Pujari, H. Xiong, F. Seela. J Org Chem, 75 (2010) 8693-8696.

The purpose of this research is to manipulate modified superparamagetnic iron oxide nanoparticles to provide a biomedical applicant for magnetic resonance imaging (MRI), drug delivery, and cancer treatment.1

The most recent work has been to aggregate the polyethylene oxide modified particles to create a network of stable nanoclusters then compare the cluster’s properties to monodisperse particles. The methodology for manipulating the particles will be to thermally cluster them then stabilize them using “click” chemistry and a bis-azide molecule to create a crosslink bridge.

Fig. 1: Schematic of imaging and hyperthermia

Fig. 3: Depiction of a modified nanoparticles cluster

Click Chemistry •  Copper-catalyzed azide-alkyne cycloaddition (CuAAC) •  Utilizing reaction to perform bis-click with modified particles and bis-azide species

Bis-Azide Synthesis7 •  Synthesized for use as crosslink agent in click reaction

Crosslinking Method •  React clustered nanoparticle with bis-azide (crosslinking bridge) •  “Bis-Click” chemistry to react azide groups with alkyne terminated polymer branches8

Fig. 5: Bis-azide reaction

Fig. 6: Schematic of crosslinking reaction with clustered nanoparticles

Fig. 4: Reaction of CuAAC6

Nanoparticles (RS-3-56): •  Iron oxide nanoparticles synthesized by thermal decomposition4

• Core size: 8.5 nm in diameter •  Modified by ligand exchange with heterobifunctional polyethylene oxide (PEO) 5

Clustering Nanoparticles •  Thermally induce particles to create clusters •  Temperature required > 60°C •  Stable size of particles at 25°C: ~ 70 nm

Fig. 2: Depiction of modified iron oxide nanoparticle

Fe3O4

PEO Alkyne

NitroDOPA

The reaction to crosslink the modified iron oxide nanoparticles using “click” chemistry and a bis-azide molecule successfully produced a crosslinking inter-particle bridge. The resulting larger sized cluster showed stability at lower temperatures, which provides evidence that the crosslink bridge successfully stabilizes the network of particles

Future research involves further characterization of the crosslinked clusters’ magnetic properties, for example relaxivity values for imaging ability. Size controllability can also be further investigated by varying temperature to observe various cluster sizes. Another possible continued investigation would be to use a larger iron oxide core sizes for the modified particles because the larger core could result in increased magnetic properties.

Fig. 7: Heating-cooling hydrodynamic size study from 20°C-70°C

Table 1: Z-Average from Fig. 6, with critical temperature of 70°C highlighted

Tempature (°C)

Z-Ave (d.nm)

Heating 20 71.5 30 85.1 40 76.0 50 70.5 60 86.5 70 113.0

Cooling 70 115.1 60 68.9 50 70.2 40 70.5 30 71.5 20 71.1

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Time (min)

Fig. 10: Particle growth versus time for crosslink reaction run at 80°C for 14 hours

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.nm)  

Temperature  

Hea/ng  

Cooling  

Fig. 11: Particle size at 25°C before and after crosslinking reaction. Respective Z-average diameter 69.77 nm and 279.5 nm

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Thermal Stability: •  Stable size from 20°C to 60°C •  Increase in size to 115 nm at 70°C

•  Proves ability to thermally induce clustering, and will use critical temperature to set conditions for crosslinking reaction

Biological Stability •  Phosphate Buffer Solution (PBS), used to match pH environment in the body

• Particles stable in titration of PBS

Fig. 9: 1H-NMR confirmation for bis-azide

Crosslinked Particles: •  Increase in size during “click” reaction, with growth rate decreasing over time

•  Particle cluster size exhibited relatively low polydispersity

•  Cluster size stable at room temperature

•  Sample species went from monodisperse particles to crosslinked cluster of particles

N3 N3

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Fig. 8: Particle size with increasing amount of PBS by volume percent