Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities

Abstract

Superparamagnetic iron oxide nanoparticles (SPION) have received immense interest for biomedical applications, with the first clinical application as negative contrast agent in magnetic resonance imaging (MRI). However, the first generation MRI contrast agents with dextran-enwrapped, polydisperse iron oxide nanoparticle clusters are limited to imaging of the liver and spleen; this is related to their poor colloidal stability in biological media and inability to evade clearance by the reticuloendothelial system. We investigate the qualitatively different performance of a new generation of individually PEG-grafted core–shell SPION in terms of relaxivity and cell uptake and compare them to benchmark iron oxide contrast agents. These PEG-grafted SPION uniquely enable relaxivity measurements in aqueous suspension without aggregation even at 9.4 T magnetic fields due to their extraordinary colloidal stability. This allows for determination of the size-dependent scaling of relaxivity, which is shown to follow a d2 dependence for identical core–shell structures. The here introduced core–shell SPION with ∼15 nm core diameter yield a higher R2 relaxivity than previous clinically used contrast agents as well as previous generations of individually stabilized SPION. The colloidal stability extends to control over evasion of macrophage clearance and stimulated uptake by SPION functionalized with protein ligands, which is a key requirement for targeted MRI.

Thermoresponsive Polypeptoid‐Coated Superparamagnetic Iron Oxide Nanoparticles by Surface‐Initiated Polymerization

“…A dense, stably anchored polypeptoid shell should allow for colloidal stability of the SPION by steric repulsion, [15,23,39] which was shown to be beneficial for SPION used as magnetic resonance contrast agent, [13] potential drug delivery vehicle [13,14,16] or magnetically actuated release vehicles. [40,41] The initial ligand replacement of oleic acid with nitrodopamine yields SPION with high initiator density that should convert into a high grafting density of the brush.…”

“…Many biomedical applications such as contrast agents or drug delivery vehicles benefit from grafting of the polymer to the surface, typically in a dense brush conformation that alters the surface properties and provides a tunable steric barrier to adsorption of proteins to the substrate. Surface grafting of polymer brushes can substantially change the physical properties of the brush such as its response to temperature .…”

“…Reports include linear homopolypeptoids such as poly(N-C3 glycine)s [8] and linear and bottlebrush co-polypeptoids by random copolymerization of either N-substituted N-carboxy anhydrides (N-ethylglycine N-carboxyanhydride (NCA) and N-butylglycine NCA) [9,10] or N-substituted N-thiocarboxy anhydrides (N-methylglycine N-thiocarboxy anhydride (NTA) and N-butylglycine NTA). [11,12] Many biomedical applications such as contrast agents [13] or drug delivery vehicles [14] benefit from grafting of the polymer to the surface, typically in a dense brush conformation that alters the surface properties and provides a tunable steric barrier to adsorption of proteins to the substrate. Surface grafting of polymer brushes can substantially change the physical properties of the brush such as its response to temperature.…”

Enhanced cellular uptake of iron oxide nanoparticles modified with 1,2-dimyristoyl-sn-glycero-3-phosphocholine

“…[1][2][3][4] The interaction between nanoparticles and cell membranes is impacted by the surface modication, charge, size and shape of the nanoparticles. [5][6][7] Phospholipids are important components of mammalian cell membranes. 8 As a typical phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) has a long double carbon chain with the zwitterion head groups containing phosphate and choline.…”

A magnetically responsive nanocomposite scaffold combined with Schwann cells promotes sciatic nerve regeneration upon exposure to magnetic field

“…[31][32][33][34] In this study, the MNPs were synthesized and the morphology was determined by TEM (Figure 2A). Figure 2B shows that MNPs were fairly uniform in distribution and the average particle diameter was 28.90±9.34 nm.…”