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 Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) 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.
Digital Object Identifier (DOI)
MD and DS acknowledge the financial support from a NCI-CNTC (National Cancer Institute Cancer Nanotechnology Training Center) predoctoral and postdoctoral traineeship (NCI 5R25CA153954).
Dan, Mo; Scott, Daniel F.; Hardy, Peter A.; Wydra, Robert J.; Hilt, J. Zach; Yokel, Robert A.; and Bae, Younsoo, "Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles" (2013). Pharmaceutical Sciences Faculty Publications. 53.