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Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

ABSTRACT: A new method to precisely monitor rapid release kinetics from polymeric particles using super paramagnetic iron oxide nanoparticles, specifically by measuring spin-spin relaxation time (T(2)), is reported. Previously, we have published the formulation of logic gate particles from an acid-sensitive poly-?-aminoester ketal-2 polymer. Here, a series of poly-?-aminoester ketal-2 polymers with varying hydrophobicities were synthesized and used to formulate particles. We attempted to measure fluorescence of released Nile red to determine whether the structural adjustments could finely tune the release kinetics in the range of minutes to hours; however, this standard technique did not differentiate each release rate of our series. Thus, a new method based on encapsulation of iron oxide nanoparticles was developed, which enabled us to resolve the release kinetics of our particles. Moreover, the kinetics matched the relative hydrophobicity order determined by octanol-water partition coefficients. To the best of our knowledge, this method provides the highest resolution of release kinetics to date.

SUBMITTER: Chan M

PROVIDER: S-EPMC3482982 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

Chan Minnie M Schopf Eric E Sankaranarayanan Jagadis J Almutairi Adah A

Analytical chemistry 20120904 18

A new method to precisely monitor rapid release kinetics from polymeric particles using super paramagnetic iron oxide nanoparticles, specifically by measuring spin-spin relaxation time (T(2)), is reported. Previously, we have published the formulation of logic gate particles from an acid-sensitive poly-β-aminoester ketal-2 polymer. Here, a series of poly-β-aminoester ketal-2 polymers with varying hydrophobicities were synthesized and used to formulate particles. We attempted to measure fluoresce ...[more]

PMID: 22891894

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Project description:BackgroundIron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.Methods and resultsIONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.ConclusionsThe presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

Project description:Folding a polymer chain into a well-defined single-chain polymeric nanoparticle (SCPN) is a fascinating approach to obtaining structured and functional nanoparticles. Like all polymeric materials, SCPNs are heterogeneous in their nature due to the polydispersity of their synthesis: the stochastic synthesis of polymer backbone length and stochastic functionalization with hydrophobic and hydrophilic pendant groups make structural diversity inevitable. Therefore, in a single batch of SCPNs, nanoparticles with different physicochemical properties are present, posing a great challenge to their characterization at a single-particle level. The development of techniques that can elucidate differences between SCPNs at a single-particle level is imperative to capture their potential applications in different fields such as catalysis and drug delivery. Here, a Nile Red based spectral point accumulation for imaging in nanoscale topography (NR-sPAINT) super-resolution fluorescence technique was implemented for the study of SCPNs at a single-particle level. This innovative method allowed us to (i) map the small-molecule binding rates on individual SCPNs and (ii) map the polarity of individual SCPNs for the first time. The SCPN designs used here have the same polymeric backbone but differ in the number of hydrophobic groups. The experimental results show notable interparticle differences in the binding rates within the same polymer design. Moreover, a marked polarity shift between the different designs is observed. Interestingly, interparticle polarity heterogeneity was unveiled, as well as an intraparticle diversity, information which has thus far remained hidden by ensemble techniques. The results indicate that the addition of hydrophobic pendant groups is vital to determine binding properties and induces single-particle polarity diversity. Overall, NR-sPAINT represents a powerful approach to quantifying the single-particle polarity of SCPNs and paves the way to relate the structural heterogeneity to functionality at the single-particle level. This provides an important step toward the aim of rationally designing SCPNs for the desired application.

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Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

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Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

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