Nanoplatform Developed to Improve Medication Delivery

A new class of “green” nanoparticles made up of a nontoxic, protein-based nanotechnology is being created to cross the blood-brain barrier noninvasively and are capable of transporting various types of pharmaceutical agents.

In an article published online May 1, 2012, in the journal PLoS ONE, Gordana Vitaliano, MD, director of the brain imaging nanotechnology group at the McLean Hospital Imaging Center (Belmont, MA, USA) reported that clathrin protein, a ubiquitous protein found in human, animal, plant, bacteria and fungi cells, has been engineered for use as a nanoparticle for in vivo research. “Clathrin has never been modified for use in vivo and offers many new and interesting possibilities for delivering drugs and medical imaging agents into the brain,” said Dr. Vitaliano.
Clathrin is the body’s major delivery vehicle responsible for delivering many different types of molecules into cells. Dr. Vitaliano thus believed that the protein’s naturally strong transport capabilities might be put to everyday medical use for drug delivery and medical imaging. “This study provides a new insight into utilizing bioengineered clathrin protein as a novel nanoplatform that passes the blood brain barrier,” said Dr. Vitaliano, who effectively attached different fluorescent labels, commonly used in imaging, to functionalize clathrin nanoparticles. “We were able to show that the clathrin nanoparticles could be noninvasively delivered to the central nervous system [CNS] in animals. The clathrin performed significantly.”

Of vital significance for future clinical applications, Dr. Vitaliano also showed that clathrin crossed and/or bypassed the blood-brain barrier without modifications or enhancers, unlike other nanoparticles. These findings open the door to exploring new and important CNS medical applications.

One important medical application for clathrin nanoparticles would be in magnetic resonance imaging (MRI). Gadolinium contrast agents are freuqently utilized to improve MRI performance. In one arrangment, Dr. Vitaliano discovered that functionalized clathrin nanoparticles performed 8,000 times better than an US Food and Drug Administration (FDA) approved MRI contrast agent (gadopentetate dimeglumine).

“Stated another way, it means 8,000 times less gadolinium might be required for achieving good MRI results. Because very low gadolinium concentrations would be required for MRI, it could significantly decrease gadolinium toxicity, which is an important issue,” explained Dr. Vitaliano. “Clathrin transported gadolinium is therefore among the most potent, biocompatible contrast agents available.”
These results in two different applications showed that clathrin offers substantial functionalization and transport flexibility. Purified clathrin nanoparticles could therefore serve as an attractive option to other medical nanoplatforms such as dendrimers, nanogels, solid lipid nanospheres, and liposomes.

Given the acute need for new types of CNS drug transport capabilities, Dr. Vitaliano stated that her research would likely be of interest to researchers involved in neuroimaging and neuroscience, in addition to radiologists, bioengineers, chemists, physicists, material scientists, biomedical researchers, and other researchers active at the front lines of imaging and drug delivery.

Looking forward, Dr. Vitaliano noted that her findings might also help other research for studying signaling pathways in different diseases that rely in whole or in part on clathrin transport, and thus may have a considerable impact in many fields.

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McLean Hospital Imaging Center