When Associate Professor of Chemical and Biomolecular Engineering Hyunjoon Kong, graduate student Cartney Smith, and colleagues set out to improve MR imaging (MRI), they turned current contrast agent technology on its head—or rather, they turned it inside out.
The new compound they designed in collaboration with Roger Adams Professor of Chemistry Steven C. Zimmerman is not only more effective, but also self-assembling. Kong is a member of the Regenerative Biology and Tissue Engineering research theme at the Institute for Genomic Biology.
When doctors perform an MRI, they administer a contrast agent: a chemical that, when injected into the bloodstream or ingested by the patient just before the MRI, improves the clarity of structures or organs in the resulting image. One common class of contrast agent, often used for imaging of blood vessels and internal bleeding, contains gadolinium, a rare-earth metal.
Recently, biomedical researchers have found ways to increase the effectiveness of certain contrast agents by associating them with nanoparticles. The contrast agent being used is packaged inside or bonded to the surface of microscopic particles, which can be designed to target certain regions of the body or prolong the agent’s activity.
Researchers are now exploring the multipurpose use of nanoparticles. If particles could be loaded with several types of contrast agents or dyes instead of one, or a contrast agent along with another type of diagnostic aid or a medication, doctors could more efficiently test for and treat conditions, and limit the number of injections received by patients.
Just like toddlers sharing a new toy, though, compounds packaged together into a nanoparticle cannot always play well together. For example, contrast agents may bind to other chemicals, reducing their effectiveness. In addition, when contrast agents are enclosed inside a nanoparticle, they may not work as well. Attempts to attach agents to the outer surface of nanoparticles via covalent formation are also problematic, as they can negatively affect the activity of the nanoparticles or the compounds that they carry.
Kong, Smith and colleagues tackled these challenges by using interactions between naturally occurring biomolecules as a guide. Many types of proteins are strongly attached to cell membranes not by covalent bonds, but by the sum of multiple weaker forces—the attraction of positive and negative charges, and the tendency of non-polar (oil-like) substances to seek each other and avoid water.
The group hypothesized that the same types of forces could be used to attach a contrast agent to the surface of a type of nanoparticle called a liposome, which resembles a little piece of cell membrane in the shape of a tiny bubble. The researchers designed a “fastener” molecule, DTPA-chitosan-g-C18, that is charged, attracting it to the liposome and binding it to the contrast agent gadolinium. A nonpolar region anchors it to the liposome membrane.
In a series of experiments reported in a recent ACS Nano article (DOI: 10.1021/nn4026228), Kong and others demonstrated that their fastener molecule readily inserted itself into the membrane of pre-made liposomes. Gadolinium stably associated with the modified nanoparticles in solution, and experiments in animal models showed that these nanoparticles produced clear diagnostic images.
“The strategy works like Velcro on a molecular level to adhere functional units to the outer leaflet of a liposome,” said Smith, who was first author on the study. “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.”
One of the difficulties of working with liposomes is their tendency to degrade inside the body. When the fastener-loaded liposomes degraded, some of the efficacy of the gadolinium was lost. In a second study published in Langmuir (DOI: 10.1021/la500412r), Kong and Smith developed a process for chemically cross-linking the components of the nanoparticle that prolonged the life of the nanoparticles in biological conditions.
The work reported in ACS Nano was a collaboration among Kong, Smith, Zimmerman, and others at the University of Illinois, as well as Dr. Sanjay Misra and researchers at the Mayo Clinic. Both studies were supported by funding from the National Institutes of Health, as well as the University of Illinois Center for Advanced Study.
Nicholas Vasi | Eurek Alert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy