Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles

Abstract

Purpose To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs). Methods Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe3O4 IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe3O4 IONPs (Citrate-IONPs). Results CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43 °C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (> 400 nm) in all aqueous media tested. No cytotoxicity was observed in a mouse brain endothelial-derived cell line (bEnd.3) exposed to CNA-IONPs up to 10 mg/mL for 30 h. Citrate-IONPs (> 0.05 mg/mL) reduced cell viability after 3 h. CNA-IONPs retained the superparamagnetic properties of entrapped IONPs, enhancing T2-weighted magnetic resonance images (MRI) at 0.02 mg/mL, and generating heat at a mild hyperthermic level (40 ~ 42 °C) with an alternating magnetic field (AMF). Conclusion Compared to citric acid coating, CNAs with a cross-linked anionic core improved particle stability and biocompatibility of IONPs, which would be beneficial for future MRI and AMF-induced remote hyperthermia applications.

Colloidal magnetic nanocrystal clusters: variable length-scale interaction mechanisms, synergetic functionalities and technological advantages

“…Adding a solvent in which the polymer was insoluble yielded small secondary structures, while adding a solvent in which the polymer is soluble allowed for larger structures embedding a large number of primary nanocrystals to be formed. Different types of molecules, as encapsulating agents of iron oxide nanoparticles, have been used, including polymers/block copolymers ( Figure 6A, B) [24,99,98,101,94], micelles ( Figure 6C) [100], polysaccharides [22,32], or hydrogels [95]. For example, aggregated iron oxide particles with controlled size have been prepared by utilizing methods based on acid/base interactions involving pre-formed nanocrystals in an organic solvent ( Figure 6C) [100].…”

Nanoparticles for Intravascular Applications: Physicochemical Characterization and Cytotoxicity Testing

“…In the recent years, increased numbers of publications appeared concerning the possible interactions between nanoparticles and endothelial cells, which are the first contact cells in the vascular wall for circulating nanoparticles. However, these reports usually focus on one type of nanosystems in the context of endothelial viability, or barrier function [6][7][8][9]. Thus, the purpose of this work was to perform comparative physicochemical and biological analyses of different types of nanoparticles intended for intravascular applications.…”

Alternating Magnetic Field-Induced Hyperthermia Increases Iron Oxide Nanoparticle Cell Association/Uptake and Flux in Blood–Brain Barrier Models

“…They can be activated by an alternating magnetic field (AMF) to generate local hyperthermia (10). Iron oxide nanoparticles are known to generate heat due to molecular vibration under AMF.…”

“…In this study, conventional citrate-coated IONPs (citrate-IONPs) and cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) (10) were used as IONP nanocarrier models to investigate the effect of AMF-induced hyperthermia on IONP permeability and flux across the BBB.…”

“…Our previous research showed that CNA-IONPs are stable for 30 h in cell culture medium in the absence and presence of AMF (10). No cytotoxicity was seen in mouse brain endothelial-derived (bEnd.3) cells exposed to ≤10 mg/mL CNA-IONPs for 30 h (10). Incorporating IONPs in CNAs significantly improved particle stability and biocompatibility compared to citrate coating, providing a promising IONP formulation.…”