skip to main content

Title: Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples
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.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
Journal of Materials Chemistry B
Page Range / eLocation ID:
3734 to 3746
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Cryopreservation technology allows long‐term banking of biological systems. However, a major challenge to cryopreserving organs remains in the rewarming of large volumes (>3 mL), where mechanical stress and ice formation during convective warming cause severe damage. Nanowarming technology presents a promising solution to rewarm organs rapidly and uniformly via inductive heating of magnetic nanoparticles (IONPs) preloaded by perfusion into the organ vasculature. This use requires the IONPs to be produced at scale, heat quickly, be nontoxic, remain stable in cryoprotective agents (CPAs), and be washed out easily after nanowarming. Nanowarming of cells and blood vessels using a mesoporous silica‐coated iron oxide nanoparticle (msIONP) in VS55, a common CPA, has been previously demonstrated. However, production of msIONPs is a lengthy, multistep process and provides only mg Fe per batch. Here, a new microporous silica‐coated iron oxide nanoparticle (sIONP) that can be produced in as little as 1 d while scaling up to 1.4 g Fe per batch is presented. sIONP high heating, biocompatibility, and stability in VS55 is also verified, and the ability to perfusion load and washout sIONPs from a rat kidney as evidenced by advanced imaging and ICP‐OES is demonstrated.

    more » « less
  2. Ferromagnetic Co 35 Fe 65 , Fe, Co, and Ni nanowires have high saturation magnetizations ( M s ) and magnetic anisotropies, making them ideal for magnetic heating in an alternating magnetic field (AMF). Here, Au-tipped nanowires were coated with polyethylene glycol (PEG) and specific absorption rates (SAR) were measured in glycerol. SAR increased when using metals with increasing M s (Co 35 Fe 65 > Fe > Co > Ni), reaching 1610 ± 20 W g −1 metal at 1 mg metal per ml glycerol for Co 35 Fe 65 nanowires using 190 kHz and 20 kA m −1 . Aligning these nanowires parallel to the AMF increased SAR up to 2010 W g −1 Co 35 Fe 65 . Next, Co 35 Fe 65 nanowires were used to nanowarm vitrified VS55, a common cryoprotective agent (CPA).Nanowarming rates up to 1000 °C min −1 (5 mg Co 35 Fe 65 per ml VS55) were achieved, which is 20× faster than the critical warming rate (50 °C min −1 ) for VS55 and other common CPAs. Human dermal fibroblast cells exposed to VS55, and Co 35 Fe 65 nanowire concentrations of 0, 1 and 2.5 mg Fe per ml all showed similar cell viability, indicating that the nanowires had minimal cytotoxicity. With the ability to provide rapid and uniform heating, ferromagnetic nanowires have excellent potential for nanowarming cryopreserved tissues. 
    more » « less
  3. null (Ed.)
    Although prior studies have investigated the effects of solution constituents, including dissolved organic matter and synthetic polymers, on nanoparticle mobility in porous media, far less attention has been directed toward evaluating the impacts of biosurfactants secreted by microorganisms on the transport and retention behavior of nanomaterials. The objective of this study was to explore the influence of rhamnolipid, a biosurfactant associated with biofilms, on the transport and retention of iron oxide nanoparticles (IONPs) in a water-saturated quartz sand. Column experiments were conducted using aerobic medium (ionic strength = 50.4 mM) or 10 mM NaCl as background electrolyte at a pore velocity of 0.43 m per day and pH 6.8 ± 0.2. In aerobic medium columns, nearly all introduced nanoparticles were retained when IONPs were injected alone, whereas the presence of 10 mg L −1 or 50 mg L −1 rhamnolipid resulted in ∼25% and ∼50% breakthrough of the injected IONP mass, respectively. Moreover, preflushing media with 50 mg L −1 rhamnolipid further increased IONP mass breakthrough by ∼30%. Similar enhancement of nanoparticle mobility by 50 mg L −1 rhamnolipid was also measured in lower ionic strength (10 mM NaCl) columns. Mathematical models that incorporated nanoparticle filter ripening and biosurfactant competitive adsorption successfully reproduced experimental observations. Modeling results predicted an order-of-magnitude decrease in IONP filter ripening rate coefficient and a three-fold drop in average IONP retention capacity in the presence of rhamnolipid, consistent with a stabilizing effect and competition for surface sites. These findings demonstrate that rhamnolipid biosurfactant can potentially enhance nanomaterial stability and mobility in subsurface environments and that these effects should be considered when evaluating the impact of biological process on nanoparticle fate and transport in porous media. 
    more » « less
  4. Background

    Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin‐azithromycin sinus stent (CASS) in vitro.


    The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly‐l‐lactic acid (PLLA) stent. In‐vitro evaluation included: (1) assessment of drug‐coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti‐biofilm activities againstPseudomonas aeruginosa.


    The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reducedP aeruginosabiofilm mass compared with bare stents and controls (relative optical density units at 590‐nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000;p< 0.001; n = 3).


    The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti‐biofilm activities againstP aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.

    more » « less
  5. We have prepared a new series of nickel phosphine phosphonate ester complexes that feature two metal-chelating polyethylene glycol (PEG) side arms. Metal binding and reactivity studies in polar solvents showed that they readily coordinate external cations, including alkali (Li + , Na + , K + ), alkaline (Mg 2+ , Ca 2+ ), transition (Sc 3+ , Co 2+ , Zn 2+ ), post-transition (Ga 3+ ), and lanthanide (La 3+ ) metals. Although olefin polymerization reactions are typically performed in non-polar solvents, which cannot solubilize +2 and +3 metal cations, we discovered that our nickel catalysts could promote ethylene polymerization in neat tetrahydrofuran. This advance allowed us, for the first time, to systematically investigate the effects of a wide range of M + , M 2+ , and M 3+ ions on the reactivity of nickel olefin polymerization catalysts. In ethylene homopolymerization, the addition of Co(OTf) 2 to our nickel-PEG complexes provided the largest boost in activity (up to 11-fold, 2.7 × 10 6 g mol −1 h −1 ) compared to that in the absence of external salts. The catalyst enhancing effects of secondary metals were also observed in studies of ethylene and polar olefin ( e.g. , propyl vinyl ether, allyl butyl ether, methyl-10-undecenoate, and 5-acetoxy-1-pentene) copolymerization. Notably, combining either Co 2+ or Zn 2+ with our nickel complexes increased the rates of polymerization in the presence of propyl vinyl ether by about 5.0- and 2.4-fold, respectively. Although further studies are needed to elucidate the structural and mechanistic roles of the secondary metals, this work is an important advance toward the development of cation-switchable polymerization catalysts. 
    more » « less