Surface Functionalization of Magnetic Iron Oxide Nanoparticles for MRI Applications - Effect of Anchoring Group and Ligand Exchange Protocol

Overview

Journal Contrast Media Mol Imaging

Specialty Radiology

Date 2011 Aug 24

PMID 21861279

Citations 31

Authors

Eric D Smolensky

Hee-Yun E Park

Thelma S Berquo

Valerie C Pierre

Affiliations

Soon will be listed here.

Abstract

Hydrophobic magnetite nanoparticles synthesized from thermal decomposition of iron salts must be rendered hydrophilic for their application as MRI contrast agents. This process requires refunctionalizing the surface of the nanoparticles with a hydrophilic organic coating such as polyethylene glycol. Two parameters were found to influence the magnetic behavior and relaxivity of the resulting hydrophilic iron oxide nanoparticles: the functionality of the anchoring group and the protocol followed for the functionalization. Nanoparticles coated with PEGs via a catecholate-type anchoring moiety maintain the saturation magnetization and relaxivity of the hydrophobic magnetite precursor. Other anchoring functionalities, such as phosphonate, carboxylate and dopamine decrease the magnetization and relaxivity of the contrast agent. The protocol for functionalizing the nanoparticles also influences the magnetic behavior of the material. Nanoparticles refunctionalized according to a direct biphasic protocol exhibit higher relaxivity than those refunctionalized according to a two-step procedure which first involves stripping the nanoparticles. This research presents the first systematic study of both the binding moiety and the functionalization protocol on the relaxivity and magnetization of water-soluble coated iron oxide nanoparticles used as MRI contrast agents.

Citing Articles

Iron Oxide Nanoparticle-Based T Contrast Agents for Magnetic Resonance Imaging: A Review.

Zhang D, Zhang J, Bian X, Zhang P, Wu W, Zuo X Nanomaterials (Basel). 2025; 15(1.

PMID: 39791792 PMC: 11722098. DOI: 10.3390/nano15010033.

Mussel-Inspired Multifunctional Polyethylene Glycol Nanoparticle Interfaces.

Casagualda C, Lopez-Moral A, Alfonso-Triguero P, Lorenzo J, Alibes R, Busque F Biomimetics (Basel). 2024; 9(9).

PMID: 39329553 PMC: 11429798. DOI: 10.3390/biomimetics9090531.

Single and Multitarget Systems for Drug Delivery and Detection: Up-to-Date Strategies for Brain Disorders.

Grosso C, Silva A, Delerue-Matos C, Barroso M Pharmaceuticals (Basel). 2023; 16(12).

PMID: 38139848 PMC: 10747932. DOI: 10.3390/ph16121721.

NMR Characterization of Polyethylene Glycol Conjugates for Nanoparticle Functionalization.

Pasek-Allen J, Wilharm R, Bischof J, Pierre V ACS Omega. 2023; 8(4):4331-4336.

PMID: 36743059 PMC: 9893458. DOI: 10.1021/acsomega.2c07669.

Mussel-inspired biomaterials: From chemistry to clinic.

Taghizadeh A, Taghizadeh M, Yazdi M, Zarrintaj P, Ramsey J, Seidi F Bioeng Transl Med. 2022; 7(3):e10385.

PMID: 36176595 PMC: 9472010. DOI: 10.1002/btm2.10385.

References

Park J, An K, Hwang Y, Park J, Noh H, Kim J . Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater. 2004; 3(12):891-5. DOI: 10.1038/nmat1251. View

Sun S, Zeng H, Robinson D, Raoux S, Rice P, Wang S . Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. J Am Chem Soc. 2004; 126(1):273-9. DOI: 10.1021/ja0380852. View

Geraldes C, Laurent S . Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media Mol Imaging. 2009; 4(1):1-23. DOI: 10.1002/cmmi.265. View

Caravan P, Ellison J, McMurry T, Lauffer R . Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem Rev. 2001; 99(9):2293-352. DOI: 10.1021/cr980440x. View

Shultz M, Reveles J, Khanna S, Carpenter E . Reactive nature of dopamine as a surface functionalization agent in iron oxide nanoparticles. J Am Chem Soc. 2007; 129(9):2482-7. DOI: 10.1021/ja0651963. View

Jung C, Jacobs P . Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging. 1995; 13(5):661-74. DOI: 10.1016/0730-725x(95)00024-b. View

Laurent S, Forge D, Port M, Roch A, Robic C, Vander Elst L . Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev. 2008; 108(6):2064-110. DOI: 10.1021/cr068445e. View

Xu C, Xu K, Gu H, Zheng R, Liu H, Zhang X . Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles. J Am Chem Soc. 2004; 126(32):9938-9. DOI: 10.1021/ja0464802. View

Cheon J, Lee J . Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. Acc Chem Res. 2008; 41(12):1630-40. DOI: 10.1021/ar800045c. View

10.

Jun Y, Lee J, Cheon J . Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. Angew Chem Int Ed Engl. 2008; 47(28):5122-35. DOI: 10.1002/anie.200701674. View

11.

Wu W, He Q, Jiang C . Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies. Nanoscale Res Lett. 2011; 3(11):397-415. PMC: 3244954. DOI: 10.1007/s11671-008-9174-9. View

12.

Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H . Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 2005; 40(11):715-24. DOI: 10.1097/01.rli.0000184756.66360.d3. View

13.

Bulte J, Brooks R, Moskowitz B, Bryant Jr L, Frank J . T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L): theory and experiment. Acad Radiol. 1998; 5 Suppl 1:S137-40; discussion S145-6. DOI: 10.1016/s1076-6332(98)80084-6. View

14.

Di Marco M, Sadun C, Port M, Guilbert I, Couvreur P, Dubernet C . Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents. Int J Nanomedicine. 2008; 2(4):609-22. PMC: 2676801. View

15.

Weissleder R, Elizondo G, Wittenberg J, Rabito C, Bengele H, Josephson L . Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology. 1990; 175(2):489-93. DOI: 10.1148/radiology.175.2.2326474. View

16.

Srinivasan B, Huang X . Functionalization of magnetic nanoparticles with organic molecules: loading level determination and evaluation of linker length effect on immobilization. Chirality. 2007; 20(3-4):265-77. DOI: 10.1002/chir.20418. View

17.

Roch A, Muller R, Gillis P . Water relaxation by SPM particles: neglecting the magnetic anisotropy? A caveat. J Magn Reson Imaging. 2001; 14(1):94-6. DOI: 10.1002/jmri.1157. View