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

• Published in: Pharmaceutical research 2013-02, Vol.30 (2), p.552-561
• Main Authors: Dan, Mo, Scott, Daniel F., Hardy, Peter A., Wydra, Robert J., Hilt, J. Zach, Yokel, Robert A., Bae, Younsoo
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biocompatible Materials - chemistry; Biocompatible Materials - toxicity; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Brain - cytology; Cell Line; Cell Survival - drug effects; Chemical Precipitation; Citrates - chemistry; Citrates - toxicity; Copolymers; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - toxicity; Drug delivery systems; Hot Temperature; Magnetic Fields; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - toxicity; Medical Law; Mice; Nanoparticles; NMR; Nuclear magnetic resonance; Particle Size; Peptides - chemistry; Peptides - toxicity; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Polyethylene Glycols - toxicity; Research Paper
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0900-8

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.