Nano targeting: Self-assembled contrast agents

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  • Published: Jun 1, 2014
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: Nano targeting: Self-assembled contrast agents

Self-assembled contrast

Image created by Janet Sinn-Hanlon, DesignGroup@VetMed, University of Illinois

The development of self-assembling nanoparticles could allow contrast agents for magnetic resonance imaging to be carried to target sites in the body much more effectively than by other means, according to US researchers.

University of Illinois at Urbana-Champaign chemical and biomolecular engineer Hyunjoon Kong, graduate student Cartney Smith and chemist Steven Zimmerman teamed up with Sanjay Misra of Mayo Clinic and colleagues to improve magnetic resonance imaging (MRI). They have now turned the concept of contrast agent technology inside out to make more effective agents that can target specific sites of interest in the body.

Contrast agents are critical to clear images and greater contrast. They are usually administered without packaging, the plain gadolinium being given in solution as a small chelate. However, associating the contrast agent with a nanoparticle has been shown by several teams to improve uptake and contrast. The Illinois team has demonstrated that binding the contrast agent exclusively on a nanoparticle shell improves the setup still further. The team is also now investigating whether or not several different types of contrast agents or dyes could be used simultaneously with another type of diagnostic aid or a medication to image and treat conditions and so reduce the total number of medical transactions, or injections, a patient needs to receive.

Bond types

Unfortunately, not all contrast agents are created equal and stuffing them into a single nanoparticle may lead to preferential binding or repulsion problems.

Kong, Smith and colleagues and Misra's team have approached the various problems by exploiting the interactions between naturally occurring biomolecules as a guide. They have looked at how different types of protein can bind strongly to cell membranes via non-covalent, electrostatic, hydrophobic and other bond types. The researchers reasoned that the same types of forces could be used to attach a contrast agent to the surface of bubble-like nanoscopic liposomes. They attached their contrast agents with a charged polymeric fastener molecule, DTPA-chitosan-g-C18, which binds it to the liposome and to the contrast agent gadolinium, a non-polar region anchors it to the liposome membrane.

Ye Gads!

They describe their proof of principle in a series of experiments published in the journal ACS Nano showing that the fastener molecule can be easily inserted into the membrane of pre-made liposomes. Gadolinium associates in a stable manner with the modified nanoparticles in solution and animal models reveal that the agents produce clear diagnostic images.

"The strategy works like Velcro on a molecular level to adhere functional units to the outer leaflet of a liposome," explains Smith. "This work represents a new material design strategy that is scalable and easily implemented. The development of improved contrast agents has the potential to directly impact patients' lives by detecting damaged blood vessels."

Of course, liposomes have a tendency to break down inside the body; which in this system means a loss of efficacy of the gadolinium contrast agent. In parallel work published in a second American Chemical Society journal Langmuir, the team developed a process for chemically cross-linking the components of the nanoparticle so that the life of the nanoparticles is prolonged under physiological conditions.

"Our next steps are to add a therapeutic component, and to further improve localization of the contrast agent at sites of interest by incorporating targeting ligands with the fastener," Smith told SpectroscopyNOW. "We ultimately hope our work can aid in early detection, as well as monitoring and treating of cardiovascular disease."

Related Links

ACS Nano, 2013, 7, 9599–9610: "A Polymeric Fastener Can Easily Functionalize Liposome Surfaces with Gadolinium for Enhanced Magnetic Resonance Imaging"

Langmuir, 2014, 30, 3697–3704: "Cross-Linkable Liposomes Stabilize a Magnetic Resonance Contrast-Enhancing Polymeric Fastener"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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