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 (T2), 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 characterize particle release kinetics via fluorescence of encapsulated Nile red to determine whether the chemistry designed into the polymers could finely tune the release kinetics in the minutes time regime; however, standard fluorescence-based techniques did not differentiate the release kinetics among our new series of polymeric particles. 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 coefficient. To the best of our knowledge, this method provides the highest resolution of release kinetics to date.

Labeling nanoparticles: Dye leakage and altered cellular uptake

“…The problem of fluorophore leakage has also been recognized by others, and their observations are largely in agreement with our results (18,19,21,22,25,26,28,(46)(47)(48). NR has repeatedly been shown to leak out of various NPs (18,19,25,26), and we concluded in a previous study that NR was taken up by cells through contact-mediated transfer within minutes after addition of PBCA-NPs (24).…”

Biodegradable Polymer Iron Oxide Nanocomposites: the Future of Biocompatible Magnetism

“…Chan et al developed a method studying nanoparticle release rates from biodegradable poly-β-aminoesters [14]. By taking advantage of the differences in spin relaxation times of SPIONs when encapsulated or freely solubilized in solution, the method could resolve differences in release rates between varied particle formulations at different pH values.…”

“…By taking advantage of the differences in spin relaxation times of SPIONs when encapsulated or freely solubilized in solution, the method could resolve differences in release rates between varied particle formulations at different pH values. The authors noted that the method outperformed traditional fluorophore release procedures by increasing the sensitivity and reproducibility of the release assay [14]. Magnetic manipulation of polymeric nanocomposites has also been shown to spatially direct nanoparticles into cellular compartments of interest such as mitochondria [15].…”

Light-triggered chemical amplification to accelerate degradation and release from polymeric particles

“…[23][24][25] Our design was inspired by the extensive literature on rates and mechanisms of ketal hydrolysis, 21,22 degradation rates of polyketals, 26 and disassembly of ketal-modified polymeric particles. [27][28][29][30][31] Ketal hydrolysis rates are known to vary with hydrophilicity, 32,33 and water accessibility affects the kinetics of disassembly and degradation of polymeric particle assemblies containing ketals either within the backbone 34,35 or as pendant groups. 36 These findings inspired hydrophobic-hydrophilic switching mechanisms to exert further control over particle disassembly and/or degradation.…”