Clinically used contrast agents for magnetic resonance imaging (MRI) suffer by the lack of specificity; short circulation time; and insufficient relaxivity. Here, a one-step combinatorial approach is described for the synthesis of magnetic lipid-polymer (hybrid) nanoparticles (MHNPs) encapsulating 5 nm ultra-small super-paramagnetic iron oxide particles (USPIOs) and decorated with Gd(3+) ions. The MHNPs comprise a hydrophobic poly(lactic acid-co-glycolic acid) (PLGA) core, containing up to ∼5% USPIOs (w/w), stabilized by lipid and polyethylene glycol (PEG). Gd(3+) ions are directly chelated to the external lipid monolayer. Three different nanoparticle configurations are presented including Gd(3+) chelates only (Gd-MHNPs); USPIOs only (Fe-MHNPs); and the combination thereof (MHNPs). All three MHNPs exhibit a hydrodynamic diameter of about 150 nm. The Gd-MHNPs present a longitudinal relaxivity (r1 = 12.95 ± 0.53 (mm s)(-1)) about four times larger than conventional Gd-based contrast agents (r1 = 3.4 (mm s)(-1)); MHNPs have a transversal relaxivity of r2 = 164.07 ± 7.0 (mm s)(-1), which is three to four times larger than most conventional systems (r2 ∼ 50 (mm s)(-1)). In melanoma bearing mice, elemental analysis for Gd shows about 3% of the injected MHNPs accumulating in the tumor and 2% still circulating in the blood, at 24 h post-injection. In a clinical 3T MRI scanner, MHNPs provide significant contrast confirming the observed tumor deposition. This approach can also accommodate the co-loading of hydrophobic therapeutic compounds in the MHNP core, paving the way for theranostic systems.
[Show abstract][Hide abstract] ABSTRACT: The complex vascular dynamics and wall deposition of systemically injected nanoparticles is regulated by their geometrical properties (size, shape) and biophysical parameters (ligand–receptor bond type and surface density, local shear rates). Although sophisticated computational models have been developed to capture the vascular behavior of nanoparticles, it is increasingly recognized that purely deterministic approaches, where the governing parameters are known a priori and conclusively describe behaviors based on physical characteristics, may be too restrictive to accurately reflect natural processes. Here, a novel computational framework is proposed by coupling the physics dictating the vascular adhesion of nanoparticles with a stochastic model. In particular, two governing parameters (i.e. the ligand–receptor bond length and the ligand surface density on the nanoparticle) are treated as two stochastic quantities, whose values are not fixed a priori but would rather range in defined intervals with a certain probability. This approach is used to predict the deposition of spherical nanoparticles with different radii, ranging from 750 to 6,000 nm, in a parallel plate flow chamber under different flow conditions, with a shear rate ranging from 50 to 90
. It is demonstrated that the resulting stochastic model can predict the experimental data more accurately than the original deterministic model. This approach allows one to increase the predictive power of mathematical models of any natural process by accounting for the experimental and intrinsic biological uncertainties.
[Show abstract][Hide abstract] ABSTRACT: While nanoparticles are usually designed for targeted drug delivery, they can also simultaneously provide diagnostic information by a variety of in vivo imaging methods. These diagnostic capabilities make use of specific properties of nanoparticle core materials. Near-infrared fluorescent probes provide optical detection of cells targeted by real-time nanoparticle-distribution studies within the organ compartments of live, anesthetized animals. By combining different imaging modalities, we can start with deep-body imaging by magnetic resonance imaging or computed tomography, and by using optical imaging, get down to the resolution required for real-time fluorescence-guided surgery.
International Journal of Nanomedicine 01/2014; 9(1):711-726. DOI:10.2147/IJN.S53717 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Magnetic nanoparticles (MNPs) accumulate at disease sites with the aid of magnetic fields; biodegradable MNPs can be designed to facilitate drug delivery, influence disease diagnostics, facilitate tissue regeneration and permit protein purification. Because of their limited toxicity, MNPs are widely used in theranostics, simultaneously facilitating diagnostics and therapeutics. To realize therapeutic end points, iron oxide nanoparticle cores (5-30 nm) are encapsulated in a biocompatible polymer shell with drug cargos. Although limited, the toxic potential of MNPs parallels magnetite composition, along with shape, size and surface chemistry. Clearance is hastened by the reticuloendothelial system. To surmount translational barriers, the crystal structure, particle surface and magnetic properties of MNPs need to be optimized. With this in mind, we provide a comprehensive evaluation of advancements in MNP synthesis, functionalization and design, with an eye towards bench-to-bedside translation.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.