Synthesis of MNP for Biological Applications

1. Synthesis of MNP for Biological Applications Carola Barrera, Ph. D. Department of Chemical Engineering University of Puerto Rico at Mayagüez

2. Magnetic Fluids Ferrofluids are colloidal suspensions of magnetic nanoparticles in a liquid carrier which can be controlled by the use of external magnetic fields. Magnetic nanoparticles (typically ~10 nm diameter) are coated with a dispersant compatible with the intended medium. Surfactants Polymers Ions Magnetic Fluid Dh

3. Motivation • Properties such as particle size, dispersion in aqueous based media, heat dissipation capacity, and manipulation using external forces have made them interesting for biomedical applications • Major challenges in this field are related to: • Single particles with a narrow size distribution Homogeneous magnetic properties Reproducibility • Stable suspension of particles in the intended medium Long term stability Physiological conditions Cell interaction with MNP Cell Culture Media

4. Synthesis of MNP Co-polymer coated MNP MNP coated with responsive polymers MNP with reactive moieties

5. Synthesis of MNP Functional Group Functionalized MNP • Typically employed functional groups interact with the surface of the particles via an equilibrium reaction between metal ions and a chelating agent such as carboxylic acids, amine groups, and phosphates. • Silane agents with alkoxy groups that are prone to hydrolysis and condensation offer an alternative to covalently graft molecules to the surface of the particles through siloxane bonds with surface metals, avoiding polymer desorption.

6. Synthesis of Functional Polymers Electrostatic Stabilized MNP N-[(3-Trimethoxysil)propyl] EDTA trisodium salt 3-aminopropyltimethoxysilane (APS) Steric Stabilized MNP Poly(ethylene glycol) Various Chitosan 2 and 10 kDa Carboxymethyl-Dextran 10 kDa

7. Not water dispersible Synthesis of MNP • MNP can be synthesized through various techniques such as co-precipitation, reverse micelles, and thermal decomposition. N2 Water ∞ Co-precipitant ∞ After 30 min T = 80C Thermal Decomposition ∞ Co-precipitation

8. Synthesis of MNP • For CoFe2O4 nanoparticles a ferrimagnetic response is observed with a coercivity of 10 kA/m while Fe3O4 nanoparticles shows a superparamagnetic response which in the absence of an external magnetic field no remanence magnetization is observed. Magnetization curve for ) CoFe2O4 and ) Fe3O4 magnetic nanoparticles embedded in paraffin • For particles suspended in hexane a Dpgv of 12 and 10 nm with a lng of 0.33 and 0.26 were obtained for CoFe2O4 and Fe3O4 respectively

9. Surface Modification of MNP After Before

10. Synthesis Functional Polymers

11. Synthesis of Functional Polymers • Carboxylic acid – PEG is obtained by room temperature oxidation of poly(ethylene glycol)’s using Jone’s reagent (CrO3/H2SO4). • With this technique PEG’s with molecular weights ranging from 550 to 100,000 can be easily oxidized to COOH-PEG with yields as high as 88%. Precipitation of chromium salts indicate the oxidation of PEG hydroxymethyl groups B. S. Lele and M. G. Kulkarni 1998

12. Surface Modifcation of MNP a) amine groups b) amide linkage IR spectrums of a) APS b) PEG-1000 and c) Dextran coated MNP DLS of MNP in deionized water

13. Stability of MNP DLS and Zeta Potential Measurements of a) APS, b) CM-dextran, c)PEG-5000 MNP on the left and Zeta potential measurements for A) CS-10 kDa, B) CS-2 kDa, and C) silane-COOH MNP

14. Stability of MNP DLS and Zeta Potential Measurements of a) PEG and b) CM-dextran coated MNP on the top left and DLS for PEG coated MNP with PEG-750 as a function of time. Table summarized the Dh for MNP coated with PEG-2000 at different temperatures.

15. Surface Modification of MNP SAR experiments at 233 kHz and 66 kA/m

16. Publications • Publications • C. Barrera, A. Herrera, Y. Zayas, C. Rinaldi, Journal of Magnetism and Magnetic Materials 321 (2009) 1397-1399. • C. Barrera, A. Herrera, C. Rinaldi, Journal of Colloid and Interface Science 329 (2009) 107-113. • A. Herrera, C. Barrera, C. Rinaldi, Journal of Materials Chemistry 18 (2008) 3650. Patent • Functionalization of Magnetic Nanoparticles with Aminopropyl-silane and Carboxymethyl-dextran – application number 12/381,073 submitted on March 6, 2009