Functionalization and peptide-based delivery of magnetic nanoparticles as an intracellular MRI contrast agent

Abstract

We report the development of functionalized superparamagnetic iron oxide nanoparticles with a PEG-modified, phospholipid micelle coating, and their delivery into living cells. The size of the coated particles, as determined by dynamic light scattering and electron microscopy, was found to be between 12 and 14 nm. The PEG-phospholipid coating resulted in high water solubility and stability, and the functional groups of modified PEG allowed for bioconjugation of various moieties, including a fluorescent dye and the Tat peptide. Efficient delivery of the functionalized nanoparticles into living cells was confirmed by fluorescence microscopy, relaxation time measurements, and magnetic resonance imaging (MRI). This demonstrates the feasibility of using functionalized magnetic nanoparticles with uniform (approximately 10 nm) sizes as an MRI contrast agent for intracellular molecular imaging in deep tissue. These micelle-coated iron oxide nanoparticles offer a versatile platform for conjugation of a variety of moieties, and their small size confers advantages for intracellular molecular imaging with minimal perturbation.

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

“…Although some microemulsion approaches produce nanoparticles that are only soluble in organic solvents, 78 these SPIO can be given water-soluble coatings that prevent agglomeration. 101 It should be noted that while it is generally accepted that microemulsion can produce SPIO with homogeneous sizes, this is dependent on the approach and precision. Further, microemulsion techniques have been criticized as an approach for synthesizing larger nanoparticles due to the formation of SPIO with poor crystallinity.…”

Magnetic microreactors for efficient and reliable magnetic nanoparticle surface functionalization

“…This expression accounts for the magnetic field generated by a wire with a uniform magnetization. The angular average convective velocity profile, instead, is defined using a semi-empirical formula, verified by fitting the results of the two dimensional simulations: (8) Where V 0 is the average velocity in the microreactor, Re is the wire Reynolds number (Re= V 0 R w / where and are the density and viscosity of water, respectively), and and are fitting parameters. It was found that a power law dependence of these constants on Peclet number (Pe=V 0 ·R w /D 0 ) was the best option.…”

“…In addition, particle surface functionalization is also time consuming due to the purification steps, which are necessary to remove un-reacted reagents and reaction side products. However, standard techniques such as centrifugation or dialysis 7,1,8 often result in irreversible aggregation. Purification by size exclusion chromatography, which is repeated after each surface functionalization step, results in suspension dilution and eventually the loss of NPs in the column.…”

Engineering imaging probes and molecular machines for nanomedicine

“…Amphiphilic polymers with a low critical micelle concentration (CMC), e.g., Poloxamer ® , Poloxamine ® and lipid-PEG copolymer, can form a stable coating layer around hydrophobic cores [98,114,119]. Amphiphilic polymer coated carbon nanotubes, polystyrene beads, quantum dots, and superparamagnetic iron oxide nanoparticles have been used in in vitro and in vivo applications [17,97,98,114,120,121]. This coating can be generalized for many hydrophobic nanocrystals because it does not rely on the reactivity of the crystal surface [98].…”

“…Hydrophobic nanocrystals are usually encapsulated with amphiphilic polymers through a film hydration process [17,97,122,123]. In this method, amphiphilic polymers and nanocrystals are first distributed in a thin film, which is often performed by dispersing all components in chloroform and evaporating the solvent with a rotary evaporator, resulting in a film with uniformly distributed components.…”