Block copolymer cross-linked nanoassemblies improve particle stability and biocompatibility of superparamagnetic iron oxide nanoparticles

Mo Dan, Daniel F. Scott, Peter A. Hardy, Robert J. Wydra, J. Zach Hilt, Robert A. Yokel, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish
Pages (from-to)552-561
Number of pages10
JournalPharmaceutical Research
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
MD and DS acknowledge the financial support from a NCI-CNTC (National Cancer Institute Cancer Nanotechnology Training Center) predoctoral and postdoctoral traineeship (NCI 5R25CA153954).


  • cross-linked nanoassemblies
  • hyperthermia
  • magnetic resonance imaging
  • nanoparticles
  • superparamagnetic iron oxide

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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