PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications - PubMed (original) (raw)

PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications

Murali Mohan Yallapu et al. Pharm Res. 2010 Nov.

Abstract

Purpose: Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, as a magnetic resonance imaging (MRI) agent, and for their ability to conjugate to an antibody.

Methods: An iron oxide core coated with oleic acid (OA) and then with OA-PEG forms a water-dispersible MNP formulation. Hydrophobic doxorubicin partitions into the OA layer for sustained drug delivery. The T(1) and T(2) MRI contrast properties were determined in vitro and the circulation of the MNPs was measured in mouse carotid arteries. An N-hydroxysuccinimide group (NHS) on the OA-PEG-80 was used to conjugate the amine functional group on antibodies for active targeting in the human MCF-7 breast cancer cell line.

Results: The optimized formulation had a mean hydrodynamic diameter of 184 nm with an ~8 nm iron-oxide core. The MNPs enhance the T(2) MRI contrast and have a long circulation time in vivo with 30% relative concentration 50 min post-injection. Doxorubicin-loaded MNPs showed sustained drug release and dose-dependent antiproliferative effects in vitro; the drug effect was enhanced with transferrin antibody-conjugated MNPs.

Conclusion: PEG-functionalized MNPs could be developed as a targeted drug delivery system and MRI contrast agent.

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Figures

Figure 1

Figure 1

Magnetic nanoparticle synthesis (A) and layering of various OA-PEG polymers on the surface of the magnetic nanoparticles (B).

Figure 2

Figure 2

Magnetic nanoparticle size changes with OA-PEG polymer coating. (A) Mean particle size in water after modification with 25–300 mg of OE-20, OE-40, or OE-80 polymers. (B) Representative transmission electron micrograph of OE-40 polymer coated MNPs. Diameter of iron-oxide core ~8 nm.

Figure 3

Figure 3

Polymer modifications to OA-MNP core confirmed by (A) FTIR and (B) TGA.

Figure 4

Figure 4

X-ray photoelectron spectra with plain, OA, and OA and PEG-OE-80 coatings.

Figure 5

Figure 5

Macrophage uptake of particles with respect to iron level in protein. (Inset) Particle size in RPMI media (data is represented as mean ± SEM, n=3, *p<0.05 compared to Feridex IV).

Figure 6

Figure 6

Magnetic resonance imaging. (A) Contrast at varying iron concentrations for OA-PEG-MNPs and Feridex IV in agar gels. T2 relaxivity (B) and T1 relaxivity (C) for OE-80 MNPs. (Data as values obtained from curve fitting and standard errors are uncertainties in fitting.)

Figure 7

Figure 7

Calculated relative iron concentration vs. time profiles of magnetic nanoparticles in a mouse carotid artery. Shown is the change in one carotid artery but both carotid arteries, and MNP injections in additional mice, showed an almost identical pattern.

Figure 8

Figure 8

Characterization and drug release of DOX-MNPs. (A) Polymer formulations modified with DOX and (B) release profile of DOX from DOX-OE-80 MNPs (data is represented as mean ± SEM, n=3).

Figure 9

Figure 9

Transferrin antibody conjugation to OE-80 MNPs. (A) Antibody conjugation to plain and DOX loaded OE-80 MNPs. (B) Transferrin and BSA binding to OE-80-Ab MNPs indicates proper orientation of transferrin antibody antigen binding sites (data is represented as mean ± SEM, n=3).

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