Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy

Abstract

Enormous efforts have been made toward the translation of nanotechnology into medical practice, including cancer management. Generally the applications have fallen into two categories: diagnosis and therapy. Because the targets are often the same, the development of separate approaches can miss opportunities to improve efficiency and effectiveness. The unique physical properties of nanomaterials enable them to serve as the basis for superior imaging probes to locate and report cancerous lesions and as vehicles to deliver therapeutics preferentially to those lesions. These technologies for probes and vehicles have converged in the current efforts to develop nanotheranostics, nanoplatforms with both imaging and therapeutic functionalities. These new multimodal platforms are highly versatile and valuable components of the emerging trend toward personalized medicine, which emphasizes tailoring treatments to the biology of individual patients to optimize outcomes. The close coupling of imaging and treatment within a theranostic agent and the data about the evolving course of an illness that these agents provide can facilitate informed decisions about modifications to treatment. Magnetic nanoparticles, especially superparamagnetic iron oxide nanoparticles (IONPs), have long been studied as contrast agents for magnetic resonance imaging (MRI). Owing to recent progress in synthesis and surface modification, many new avenues have opened for this class of biomaterials. Such nanoparticles are not merely tiny magnetic crystals, but potential platforms with large surface-to-volume ratios. By taking advantage of the well-developed surface chemistry of these materials, researchers can load a wide range of functionalities, such as targeting, imaging and therapeutic features, onto their surfaces. This versatility makes magnetic nanoparticles excellent scaffolds for the construction of theranostic agents, and many efforts have been launched toward this goal. In this Account, we introduce the surface engineering techniques that we and others have developed, with an emphasis on how these techniques affect the role of nanoparticles as imaging or therapeutic agents. We and others have developed a set of chemical methods to prepare magnetic nanoparticles that possess accurate sizes, shapes, compositions, magnetizations, relaxivities, and surface charges. These features, in turn, can be harnessed to adjust the toxicity and stability of the nanoparticles and, further, to load functionalities, via various mechanisms, onto the nanoparticle surfaces.

Figure 1

IONPs coated with a) a tri-block copolymer and b) dopamine-plus-HSA to confer water solubility and functional extendibility.

Figure 2

a) TEM bright field image of mPEG-b-PCL/MONP micelles; b) AFM height image of Alkyl-PEI2k-IONPs; c) hysteresis loops of the MONP containing micelles measured at 300 K (inset shows a zoomed-in plot between − 2 kOe and 2 kOe magnetic field); d) T₂ relaxation rates (1/T₂, s⁻¹) of Alkyl-PEI2k-IONP nanocomposites as a function of iron concentration (mM) for different polymer/SPIO ratios at (a) 0.6; (b) 1.2; (c) 2.5.

Figure 3

Alkyl-PEI2k-IONP nanocomposites adsorbed on polyelectrolyte covered SiO₂ nanotemplates with a) higher and b) lower anchoring density. (Scale bar = 100 nm)

Figure 4

a) Phantom studies with HSA and phospholipid-coated MONPs at the same concentrations. Due to existence of a hydrophobic coating zone between the particle surface and surrounding water molecules, phospholipid coated MONPs tend to have a less prominent T₁ reducing effect. b) r₁ relaxivity evaluation from the results of a).

Figure 5

In vivo MR imaging with a) normal mice and b) an orthotropic Huh7 hepatocarcinoma model after injection with PVP-IO-37 and Feridex. Arrow points to tumor.

Figure 6

a) Conjugating RGD onto 4-methylcatechol coated IONP surface. b) High resolution TEM images of the IONPs. c–e) MR images taken after IONP injection on a U87MG xenograft model. c) without NPs, d) with c(RGDyK)-IONPs, and e) with c(RGDyK)-IONPs and with blocking dosage of c(RGDyK). f–g) Prussian blue staining on tumor tissue samples from d) and e). Arrow points to tumor.

Figure 7

HINP-loaded macrophages were injected into a stroke model (upper right) and xenograft tumor model (lower right). Such exogenous macrophages accumulated in the areas of diseases and were detected by MRI.

Figure 8

MRI/NIRF/PET tri-modal imaging (a, NIRF; b, PET; c, MRI) with HINPs that were conjugated with both ⁶⁴Cu-DOTA and Cy5.5.