Nanostructures are beginning to be employed in biomedical applications. However, the materials must often be coated and stabilized with other substances, such as polymers, which then define the nanomaterials' pharmacokinetics and pharmacodynamics.

A team led by Hongjie Dai has now shown that as well as being biocompatible and highly stable, carbon nanotubes suspended by PEGylated polymers can remain in the bloodstream for long periods. This is in contrast to previously functionalized nanomaterials that suffer from rapid uptake by reticuloendothelial systems found in the liver, spleen, lymph nodes and bone marrow. This reduces circulation time and the effective dose for imaging contrast or drug delivery.

"Our polymer-functionalized nanomaterials, especially gold nanoparticles and nanorods, show improved stability compared with their traditionally functionalized (thiol-PEG) counterparts," team member Scott Tabakman told "This result means that the structures could be taken up into tumours by enhanced permeability and retention (EPR) effects, something that may be advantageous for targeted molecular imaging and therapy owing to increased contact with target receptors."

"Half-life" of over 20 hours
The polymer-coated nanotubes have a blood circulation "half-life" of 22.1 hours when intravenously injected into mice. This far exceeds the previous record of 5.4 hours.

The researchers made the PEGylated branched polymers via amidation chemistry, combining hydrophobic and hydrophilic components. The hydrophobic components passively associate with nanomaterials via intermolecular forces during simple sonication and dialysis procedures, explains Tabakman. They used a variety of surfactants based on the biocompatible backbones gamma-poly(glutamic acid) and poly(maleic) anhydride.

The team now plans to further elucidate the mechanisms that yield long-circulating nanomaterials. "We also hope to demonstrate improved efficacy for in vivo imaging and therapeutic applications using these PEGylated branched polymers," said Tabakman.

The work was published in the Journal of the American Chemical Society.