Monodisperse magnetic nanoparticles for theranostic applications

Abstract

Effective medical care requires the concurrent monitoring of medical treatment. The combination of imaging and therapeutics allows a large degree of control over the treatment efficacy and is now commonly referred to as "theranostics". Magnetic nanoparticles (NPs) provide a unique nanoplatform for theranostic applications because of their biocompatibility, their responses to the external magnetic field, and their sizes which are comparable to that of functional biomolecules. Recent studies of magnetic NPs for both imaging and therapeutic applications have led to greater control over size, surface functionalization, magnetic properties, and specific binding capabilities of the NPs. The combination of the deep tissue penetration of the magnetic field and the ability of magnetic NPs to enhance magnetic resonance imaging sensitivity and magnetic heating efficiency makes magnetic NPs promising candidates for successful future theranostics. In this Account, we review recent advances in the synthesis of magnetic NPs for biomedical applications such as magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH). Our focus is on iron oxide (Fe(3)O(4)) NPs, gold-iron oxide (Au-Fe(3)O(4)) NPs, metallic iron (Fe) NPs, and Fe-based alloy NPs, such as iron-cobalt (FeCo) and iron-platinum (FePt) NPs. Because of the ease of fabrication and their approved clinical usage, Fe(3)O(4) NPs with controlled sizes and surface chemistry have been studied extensively for MRI and MFH applications. Porous hollow Fe(3)O(4) NPs are expected to have similar magnetic, chemical, and biological properties as the solid Fe(3)O(4) NPs, and their structures offer the additional opportunity to store and release drugs at a target. The Au-Fe(3)O(4) NPs combine both magnetically active Fe(3)O(4) and optically active Au within one nanostructure and are a promising NP platform for multimodal imaging and therapeutics. Metallic Fe and FeCo NPs offer the opportunity for probes with even higher magnetizations. However, metallic NPs are normally very reactive and are subject to fast oxidation in biological solutions. Once they are coated with a layer of polycrystalline Fe(3)O(4) or a graphitic shell, these metallic NPs are more stable and provide better contrast for MRI and more effective heating for MFH. FePt NPs are chemically more stable than Fe and FeCo NPs and have shown great potential as contrast agents for both MRI and X-ray computed tomography (CT) and as robust probes for controlled heating in MFH.

Figure 1

Schematic illustration of (A) a single domain magnetic NP with its magnetization pointing to one direction, (B) a group of single domain magnetic NPs aligned along a magnetic field direction, (C) the hysteresis loop of a group of ferromagnetic NPs, and (D) the hysteresis loop of a group of superparamagnetic NPs.

Figure 2

(A) Schematic illustration of the chemical synthesis of Fe₃O₄ NPs, (B) TEM image of a 16 nm Fe₃O₄ NP assembly, and (C) Hysteresis loops of the 16 nm Fe₃O₄ NP assembly measured at 10 K and 300 K. Adapted with permission from references and .

Figure 3

(A) Schematic illustration of the growth of Au-Fe₃O₄ NPs. TEM images of the (B) 6 nm Au NPs and (C) 6–17 nm Au-Fe₃O₄ NPs. Adapted with permission from references and .

Figure 4

(A) Schematic illustration of the formation of FePt NPs from the decomposition of Fe(CO)₅ and reduction of Pt(acac)₂. TEM images of (B) the 6 nm FePt NPs and (C) the 9 nm FePt NPs. Adapted with permission from references , and .

Figure 5

(A) TEM images of the MnFe₂O₄ NPs (scale bar, 50 nm), (B) T₂-weighted MR images of the corresponding MnFe₂O₄ NPs, (C) color maps of the MR images, and (D) plots of NP size versus relaxivity. Reproduced with permission from reference .

Figure 6

Color maps of T₂-weighted MR images of a mouse implanted with the cancer cell line NIH3T6.7 at different time points after injection of the MnFe₂O₄-Herceptin (A–C) and the Fe₃O₄-Herceptin (D–E) conjugates. Reproduced with permission from reference .

Figure 7

(A) Schematic illustration of the coupling of c(RGDyK) peptide to Fe₃O₄ NPs. MRI of the cross section of the U87MG tumors implanted in mice, (B) without NPs, (C) with the injection of 300 µg of c(RGDyK)-Fe₃O₄ NPs. Adapted with permission from reference .

Figure 8

(A) Schematic illustration of the surface functionalization of the Au-Fe₃O₄ NPs, (B) T₂-weighted MRI of (i) 20 nm Fe₃O₄, (ii) 3 nm – 20 nm Au-Fe₃O₄, (iii) 8 nm – 20 nm Au-Fe₃O₄ NPs, and (iv) A431 cells labeled with 8 nm – 20 nm Au-Fe₃O₄ NPs. (C) Reflection image of the 8 nm – 20 nm Au-Fe₃O₄ labeled A431 cells. Adapted with permission from reference .