Biocompatibility established for therapeutic nanoparticles

April 21, 2011

Investigators at the Stanford University School of Medicine have shown that gold-centered spheres smaller than viruses are safe when administered by two alternative routes in a mouse study.

The study is the first-ever successful demonstration of the safety of a new class of agents: tiny gold balls that have been coated with materials designed to be detected with very high sensitivity, then encased in see-through silica shells and bound to polyethylene glycol molecules to make them more biologically friendly. Molecules that home in on cancer cells can be affixed to them. The resulting nanoparticles measure 100 nanometers in diameter.

The investigators administered these nanoparticles to two groups of mice, each consisting of 30 male and 30 female animals, and assessed toxicity in a variety of ways. In each case, the dose was 1,000 times as large as would be required to get a clear signal from the nanoparticles.

They monitored the test animals’ blood pressure, electrocardiograms, and white-blood-cell counts. They examined several tissues for increases in the expression of antioxidant enzymes or pro-inflammatory signaling proteins, which would suggest physiological stress on the animals’ cells. They stained tissues with dyes that flag dying cells.

These inspections yielded virtually no signs of stress to any tissues, and none at all by two weeks after the time of administration. Importantly, the team inspected tissues via electron microscopy to find out where the gold-containing particles had lodged themselves. They found no gold anywhere outside the bowel, indicating that the nanoparticles remained confined to that organ and thus, when rectally administered, posed no threat of systemic toxicity. Furthermore, the nanoparticles were quickly excreted.

In related news, researchers at Rice University and Texas A&M have discovered a way to combine proteins with a transcription factor derived from fruit flies and then draw it into fine, strong, biodegradable, and nontoxic strands that can be woven into any configuration.

The team used gene-fusion techniques to create chimeras (proteins that are fused into a single polypeptide) by combining Ubx (a 80-amino-acid module) with fluorescent and luminescent proteins to see if they remained functional. The combined materials stayed together as a unit and formed a film on water. Drawn into fibers and put under a microscope, Ubx combined with enhanced green fluorescent protein (EGFP) kept its bright green color.

The researchers were able to make patterns with strands generated by the chimeras by twisting red and green fluorescent proteins into candy cane-like tubes, or lacing them on a frame.

The material might be useful for replacing damaged nerves, says Sarah Bondos. ”We should be able to stimulate cell attachment and nerve growth along the middle and factors on the ends to enhance attachment to existing nerve cells, to tie it into the patient. It really is pretty exciting.”

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