Low Power Radiofrequency-Induced Release of Small Molecules from Iron Oxide-Polymer Core-Shell Composite Nanoparticles
Final Report Abstract
The overarching goal of the project was to establish the radiofrequency (RF)-triggered small molecules release systems based on the mechanical agitation of polyethylene glycol (PEG) shells of RF-sensitive Fe3O4 nanoparticles (NPs), placed under an alternating magnetic field (AMF). Within the scope of this research project, three major objectives were undertaken: (i) formation of the iron oxide-core/polymer-shell nanocomposites of different sizes and polymer immobilization strategies as nanocarriers for various drugs/molecules; (ii) understanding the mechanical response and stability of the polymer coatings under applied RF; (iii) investigation of the drugs loading and release under an AMF from the variety of prepared nanocarriers. In the first part of the project, a variety of the iron oxide-polymer nanocomposites of Fe3O4 cores in the size of d=20 nm were synthesized. It was assumed that in its effort to align with an AMF, the Fe3O4 cores of d>15 nm would tumble, providing kinetic energy to the polymeric shell and the encapsulated drug molecules, and helping them to overcome the electrostatic interactions, keeping them within the coating. This added kinetic energy was supposed to agitate the polymeric layer, and thus enable drugs to be liberated from the NPs without unwanted heat generation, which is normally dominant for the Fe3O4 NPs of d smaller than 15 nm. All the synthesized iron oxide-polymer nanocomposites were subsequently exposed to RF in order to understand their mechanical behavior and the associated molecular release processes. The studies were conducted on Fe3O4-PEG, Fe3O4-Ner-PEG, Fe3O4-PMAO-PEG and Fe3O4-P(PEGMA) nanocomposites. The samples were exposed to an AMF of RF for different periods of time. It is important to highlight that there was no unwanted heat generation detected in any case, pointing at the preferred mechanical activation of the magnetic NPs. Subsequently, two most promising and most stable systems were chosen for further studies on drugs loading and release under applied RF. Fe3O4-PEG and Fe3O4-PMAO-PEG of different molecular mass of polymers were tested. Doxorubicin was applied as the model molecule for Fe3O4-PEG nanocomposites, mainly because of its intrinsic fluorescence, which serves as a valuable tool in the drug release studies. Fe 3O4-PMAO-PEG nanocomposites were made of an additional hydrophobic layer (PMAO), needed to incorporate the drugs more efficiently. In this case, hydrophobic curcumin was chosen as the loading molecule. In summary, it was proven that the Fe3O4 NPs of d>15 nm agitated the polymeric layer surrounding them, which led to the release of incorporated drug molecules without unwanted heat generation. This phenomenon was time dependent and differed with variation of molecular mass of PEG and the way of its immobilization, as well as the frequency of the applied AMF. We did not only show that the whole PEG molecules were detached from Fe3O4 cores, but we also observed a minor bond scission of the PEG molecules themselves. These foundlings help to understand the mechanism underlying the PEG detachment from Fe 3O4 NPs under a magnetic field of low power. The results implied that the core-shell Fe3O4-PEG nanocomposites of core d>15 nm did not generate high temperatures under the applied AMF and could be a promising carrier for small molecules/drugs.
Publications
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Brownian Relaxation Shakes and Breaks Magnetic Iron Oxide‐Polymer Nanocomposites to Release Cargo. Small, 20(4).
Izak‐Nau, Emilia; Niggemann, Louisa P. & Göstl, Robert
