Clickable magnetic nanoparticles - a new tool for magnetic hyperthermia

Abstract

Magnetic hyperthermia (MH), based on the ability of magnetic nanoparticles (MNPs) to generate heat when exposed to alternating magnetic fields (AMF) is a very active area of research, especially for the development of new therapeutic solutions for cancer treatment. Recently, our team has initiated a new research line focused on the use of bioorthogonal click chemistry for magnetic hyperthermia studies applied using MNPs covalently attached to cell membranes. Our interest lies in the sub-lethal version of MH, which we believe is a powerful tool to induce a controlled and localized heating of the cell membrane (“hotspots”). This could produce temporal changes in the membrane biophysical properties, which can be used for enhanced delivery of therapeutics. Bioorthogonal strain-promoted “click” [3 + 2] azide-alkyne cycloaddition (SPAAC) reaction uses the ring strain to activate the alkyne, thus avoiding the use of the cytotoxic Cu(I) catalyst typically employed for standard “click” azide-alkyne cycloadditions (CuAAC). Despite its numerous applications in biology and biochemistry, SPAAC is still relatively new for nanotechnology applications. Herein, we report a simple functionalization protocol to obtain water-soluble MNPs suitable for SPAAC click chemistry. Hydrophobic 12 nm iron oxide MNPs were synthesized following a seed-mediated thermal decomposition methodology and transferred to water by coating with a fluorescent amphiphilic polymer (poly(maleic anhydride-alt-1- octadecene), PMAO-TAMRA).5 The MNPs were further functionalized step-wise with polyethyleneglycol (PEG) or a glucopyranoside derivative (Glc) to increase colloidal stability and with a cyclooctynylamine derivative. We have tested their reactivity towards azide-functionalized surfaces, demonstrating their potential as bioorthogonal probes. We are currently working on the incorporation of the “clickable” MNPs on more complex substrates (azide-modified lipid bilayers as simplified models of animal cell membranes). Studies regarding the cytotoxicity of the MNPs and their covalent attachment on living cell membranes are also underway.