PEG-Stabilized Core–Shell Nanoparticles: Impact of Linear versus Dendritic Polymer Shell Architecture on Colloidal Properties and the Reversibility of Temperature-Induced Aggregation

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely used experimentally and also clinically tested in diverse areas of biology and medicine. Applications include magnetic resonance imaging, cell sorting, drug delivery, and hyperthermia. Physicochemical surface properties are particularly relevant in the context of achieving high colloidal nanoparticle (NP) stability and preventing agglomeration (particularly challenging in biological fluids), increasing blood circulation time, and possibly targeting specific cells or tissues through the presentation of bioligands. Traditionally, NP surfaces are sterically stabilized with hydrophilic polymeric matrices, such as dextran or linear poly(ethylene glycol) brushes. While dendrimers have found applications as drug carriers, dispersants with dendritic ("dendrons") or hyperbranched structures have been comparatively neglected despite their unique properties, such as a precisely defined molecular structure and the ability to present biofunctionalities at high density at the NP periphery. This work covers the synthesis of SPIONs and their stabilization based on poly(ethylene glycol) (PEG) and oligo(ethylene glycol) (OEG) chemistry and compares the physicochemical properties of NPs stabilized with linear and dendritic macromolecules of comparable molecular weight. The results highlight the impact of the polymeric interface architecture on solubility, colloidal stability, hydrodynamic radius, and thermoresponsive behavior. Dendron-stabilized NPs were found to provide excellent colloidal stability, despite a smaller hydrodynamic radius and lower degree of soft shell hydration compared to linear PEG analogues. Moreover, for the same grafting density and molecular weight of the stabilizers, OEG dendron-stabilized NPs show a reversible temperature-induced aggregation behavior, in contrast to the essentially irreversible aggregation and sedimentation observed for the linear PEG analogues. This new class of dendritically stabilized NPs is believed to have a potential for future biomedical and other applications, in which stability, resistance to (or reversible) aggregation, ultrasmall size (for crossing biological barriers or inclusion in responsive artificial membranes), and/or high corona density of (bio)active ligands are key.

Layer-by-layer nanoencapsulation of camptothecin with improved activity

“…Low density corona and higher length of grafted PEG chains can favor aggregation of nanoparticles, as it was recently shown for gold and super paramagnetic iron oxide nanoparticles (Cheng and Cao, 2011; Gillich et al, 2013). …”

Endocytosis and exocytosis of nanoparticles in mammalian cells

“…Pre-coating of the nanoparticle surface with stabilizing molecules such as polyethylene glycol (PEG), deoxyribonucleic acid (DNA), and albumin has been utilized to reduce ionic strength and prevent nanoparticles from aggregation or agglomeration in the biological solutions. [12][13][14] Additionally, individual nanoparticles can be naturally coated with various biomolecules, forming the nanoparticleprotein complex, when solubilized in biological solutions. The stability lifetimes of the nanoparticle-protein complexes range from hours to days in the biological solutions.…”

A simple straightforward thermal decomposition synthesis of PEG-covered Gd 2 O 3 (Gd 2 O 3 @PEG) nanoparticles

“…PEG is a stabilization agent which prevents agglomeration between nanoparticles. However in high temperature synthesis, the high molecular weight of PEG releases a lot of CO 2 gas which contributes a high surface energy to the nanoparticles leading to increased agglomeration [39,40].…”