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Therapeutic blood purification using functionalized core/shell nanomagnets

Introduction

Direct and rapid removal of pathogens or noxious metabolites from a patient is the most straightforward cure imaginable. Dialysis and plasma filtration/exchange are the current broadly applicable methods to perform a direct removal of disease-causing factors from a patient. We describe the use of stable nanomagnets to rapidly and selectively remove heavy metal ions, overdosed steroid drugs and proteins from human blood. This nanomagnet-based purification method avoids fouling of filter membranes and benefits from a high external surface area, and a correspondingly fast diffusion.

Methods

Nanomagnets equipped with heavy metal complexants, digoxin antibody fragments and entire human IL-6 antibodies were added to a series of blood samples. The nanomagnets scan blood by Brownian motion and capture their target. Afterwards, a small magnet was placed at the sample tube wall accumulating the nanomagnets in the pole region of the external magnet. The purified supernatant can then easily be decanted. The concentrations of lead, digoxin and IL-6 in blood samples were determined by standard clinical methods. Blood integrity was observed by rotation thromboelastography and monitoring of serum potassium, lactate dehydrogenase, bilirubin and haptoglobin levels. To measure the biological relevance of the IL-6 removal, the effect on caspase-3 activation was assessed in camptothecin-stimulated neutrophils.

Results

A significant decrease of lead, digoxin and IL-6 levels was measured after the blood purification procedure. The extraction using nanomagnets was in clear dose-effect dependence and could be accurately titrated. Treatment with nanomagnets did not significantly affect the integrity of blood and all levels remained in the clinical norm range. Caspase-3 assays showed a reduced anti-apoptotic effect after IL-6 removal, underlining the biological relevance of the achieved removal efficiency.

Conclusions

We demonstrate the extraction of lead, digoxin and IL-6 from whole blood as an example for the rapid treatment of heavy metal poisoning, drug overdosing and severe inflammation. The presented direct blood extraction could be combined with existing therapeutic strategies and may have major implications on the treatment of severe intoxications, sepsis (specific filtering of cytokines or toxins) [1], metabolic disorders (thyreotoxicosis) and autoimmune diseases.

References

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Correspondence to IK Herrmann.

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Herrmann, I., Urner, M., Koehler, F. et al. Therapeutic blood purification using functionalized core/shell nanomagnets. Crit Care 14, P411 (2010). https://doi.org/10.1186/cc8643

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Keywords

  • Digoxin
  • External Surface Area
  • Blood Purification
  • Heavy Metal Poisoning
  • Haptoglobin Level