Magnetic nanoparticles in MR imaging and drug delivery

Abstract

Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research.

Figure 1

MNP structures and coating schemes. (A) End-grafted polymer coated MNP. (B) MNP fully encapsulated in polymer coating. (C) Liposome encapsulated MNP. (D) Core-shell MNP. (E) Heterodimer MNP.

Figure 2

MNP possessing various ligands to enable multifunctionality from a single nanoparticle platform.

Figure 3

Confocal fluorescent images of cells incubated with chlorotoxin-targeted iron oxide nanoparticles conjugated to Cy5.5. A: rat cardiomyocytes (rCM) representing normal cells. B: 9L glioma cells. C: MR phantom image of 9L (top) and rCM (bottom) cells cultured with the chlorotoxin-targeted nanoparticles (4.7 T, spin echo pulse sequence, TR 3000 ms, TE 30 ms) [19]. Reproduced with permission of the American Chemical Society.

Figure 4

Illustration of tissue specific delivery of MNPs through active targeting facilitated by “leaky” vasculature. (A) Internalization of nanoparticles by (A) receptor-mediated endocytosis and formation of an endosome. (B) Endosomal acidification by proton pumps results in elevated osmotic pressure, swelling, and (C) rupture of the endosome allowing for release of the nanoparticle and conjugated therapeutic agents.

Figure 5

MRI anatomical image of a mouse in the (a) coronal plane with the dotted line displaying the approximate location of the axial cross sections displayed in (c) and (d). Anatomical image in the (b) sagittal plane displaying the location of the 9L xenograft tumor. Change in R2 relaxation values for the tumor regions (superimposed over anatomical MR images) for mouse receiving (c) non-targeting PEG coated iron oxide nanoparticles and (d) CTX-targeted PEG coated iron oxide nanoparticles 3 hrs post nanoparticle injection. Reproduced with permission of the Wiley-VCH Verlag GmbH & Co.