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

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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.

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Acknowledgments and Disclosures

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

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA

    Mo Dan, Daniel F. Scott, Robert A. Yokel & Younsoo Bae

  2. Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky, 40536, USA

    Mo Dan & Robert A. Yokel

  3. Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, 40536, USA

    Peter A. Hardy

  4. Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky, 40506, USA

    Robert J. Wydra & J. Zach Hilt

  5. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky, 40536-0596, USA

    Younsoo Bae

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  1. Mo Dan
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Dan, M., Scott, D.F., Hardy, P.A. et al. Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles. Pharm Res 30, 552–561 (2013). https://doi.org/10.1007/s11095-012-0900-8

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  • DOI: https://doi.org/10.1007/s11095-012-0900-8

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