Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples

Jacqueline L Pasek-Allen, Randall K Wilharm, Zhe Gao, Valerie C. Pierre, John C. Bischof

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8 Scopus citations


New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches. Using cryoprotective agents (CPAs), aqueous solutions with organic components such as DMSO, propylene glycol, and added salts and sugars, organs can be used to vitrify and store organs at −140 °C. When needed, these organs can be rewarmed in a rapid and uniform manner if CPAs are supplemented with iron oxide nanoparticles (IONPs) in an applied radiofrequency field. Speed and uniformity of warming are both IONP concentration and CPA suspension dependent. Here we present a coating method of small molecule phosphonate linker (PLink) and biocompatible polymer (i.e. polyethylene glycol PEG) that tunes stability and increases the maximum allowable concentration of IONPs in CPA suspension. PLink contains a phosphonate 'anchor' for high irreversible binding to iron oxide and a carboxylic acid 'handle' for ligand attachment. PLink-PEG removes and replaces the initial coating layer of commercially available IONPs (EMG1200 (hydrophobic) and EMG308 (hydrophilic) Ferrotec, Inc., increasing colloidal stability and decreasing aggregation in both water and CPAs, (verified with dynamic light scattering) from minutes (uncoated) to up to 6 days. Heating properties of EMG1200, specific absorption rate (SAR), measured using an applied field of 360 kHz and 20 kA m−1, increased from 20 to 180 W per g Fe with increasing PLink-PEG5000. PEG replacing the initially hydrophobic coating decreased aggregation in water and CPA, consistent with earlier studies on heating performance. Furthermore, although the size is minimized at 0.20 mol PEG per g Fe, heating is not maximized until concentrations above 0.43 mol PEG per g Fe on EMG1200. SAR on hydrophilic EMG308 was preserved at 400 W per g Fe regardless of the amount of PLink added to the core. Herein concentrations of IONP in VS55 (common CPA) significantly above our previous capabilities, sIONP at 10 mg Fe per mL, was reached, 25 mg Fe per mL of 308-PEG5000 and 60 mg Fe per mL of 1200-PEG5000, approaching stock EMG308 in water, 60 mg Fe per mL. Furthermore, at these concentrations cryopreserved Human dermal fibroblast cells were successfully nanowarmed (at applied fields described above), with higher viability as compared to convective rewarming in a water bath and heating rate close to 200 °C min−1, 2.5 times faster than our current system. Using PLink as the coating method allowed for higher concentrations of IONPs to be successfully suspended in CPA without affecting the heating ability. Additionally, the model ligand, PEG, allowed for increased stability over time in nanowarming experiments.

Original languageEnglish (US)
JournalJournal of Materials Chemistry B
Issue number19
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
The authors thank Dr Qi Shao for help with the HDF cell culture, Todd Rappe, Dr Gopinath Tata at the Minnesota NMR Center for help with HRMAS NMR, Dr Raj Suryanarayanan for use of the TGA and Dr Jon Rainier and Dr Rameshu Rallabandi for useful discussions and training. They also thank UMN's Department of Earth Science, and Institute for Rock Magnetism for providing instruments and assistance in characterization. This work was funded by 5 F31 DK124968-02, NSF EEC 1941543, R01 HL135046, and R01 DK117425. Research reported in this publication was supported by the Office of the Vice President of Research, College of Science and Engineering, and the Department of Chemistry at the University of Minnesota.

Publisher Copyright:
© 2022 The Royal Society of Chemistry


  • Cryopreservation/methods
  • Cryoprotective Agents/chemistry
  • Humans
  • Ligands
  • Magnetic Iron Oxide Nanoparticles
  • Organophosphonates
  • Water

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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