Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researcher lights the way to better drug delivery

12.09.2006
A Purdue University researcher has explained for the first time the details of how drugs are released within a cancer cell, improving the ability to deliver drugs to a specific target without affecting surrounding cells.

"As a general strategy, the indiscriminate delivery of drugs into every cell of the body for the treatment of a few specific pathologic cells, such as cancer cells, is a thing of the past," said Philip Low, the Ralph C. Corley Distinguished Professor of Chemistry. "Most new drugs under development will be targeted directly to the pathologic, disease-causing cells, and we have shed light on the details of one mechanism by which this is achieved."

An understanding of the cellular process that leads to the release of targeted drugs is a major advancement for the field, he said.

"This will help others interested in targeted drug therapy," said Low, who also is founder and chief science officer of Endocyte Inc., a Purdue Research Park-based company. "The knowledge applies not only to the treatment of cancer. The understanding of how to deliver and unload a cancer drug can be extrapolated to all sorts of other diseased cells. The uptake pathways are similar in cells involved in arthritis, multiple sclerosis, psoriasis and Crohn's disease."

Interest in how drugs are released after they enter their targeted cell led Low and his team to develop a color-coded method to visualize the cellular mechanisms. Jun Yang, a postdoctoral research associate in Low's research group, together with Ji-Xin Cheng, an assistant professor in the Department of Biomedical Engineering, and his graduate student Hongtao Cheng, developed this method using a technique called fluorescence resonance energy transfer imaging.

"The drug turns from red to green when it is released inside the cell, clearly illuminating the process," Yang said. "This is the first optical method to be developed to monitor this release. The main promise of this method is that it does not damage the cells being studied. Therefore, we are able to observe the process under true physiological conditions and watch it right as it is happening."

This research, funded by Endocyte, will be detailed in a paper in Tuesday's (Sept. 12) issue of the Proceedings of the National Academy of Sciences and is currently available online.

In targeted drug therapy, drugs are linked to molecules that are used in excess by pathologic cells, for example a required nutrient, in order to transport drugs directly to the targeted cells while avoiding significant delivery of the toxic drug to normal cells. A commonly used agent, referred to as a ligand, is the vitamin folic acid. Cancer cells need folic acid to grow and divide and, therefore, have developed abundant receptors to capture it. These receptors are largely absent in normal cells. This means folic acid, and the drug linked to it, are attracted to the pathologic cells and are harmless to healthy cells, Low said.

Low led the team that discovered this folate-targeted treatment method in 1991 and the receptor-targeted technology is proprietary to Endocyte.

"It is desirable to have the drug released from the ligand, folic acid, once the folate-linked complex enters the cell," Yang said. "This 'conditional drug release' is usually realized by attaching folate to the drug through a linker that falls apart inside the cell. There were several linkers in common use, but with mixed efficiency. In this study we undertook to interrogate the full details of this breakdown process."

Yang examined receptor endocytosis, the process by which cells absorb materials — such as a drug attached to folic acid — that have been captured at special sites, called receptors, on the cell surface. The compound is then broken down and processed, releasing the drug.

One of the key mechanisms of this breakdown is disulfide reduction, which involves the breaking of chemical bonds. It was thought that disulfide reduction relied on the movement of the material along microtubules, hollow tubelike structures, and fusion with special digestive-enzyme containing compartments within the cell called lysosomes. However, the research showed that disulfide reduction occurred even when such components were removed from the process.

By inactivating different cellular components, Yang discovered which components are essential to the disulfide reduction process.

"It was surprising to learn that many other components of the cell, aside from those previously assumed to be responsible, were capable of releasing the drug from folic acid," Yang said. "This significantly increases the opportunity for the drug to be released. For instance, we used to believe it had to get to a specific location to be released, and now we know it can happen almost anywhere during endocytosis."

The mechanisms, locations and cellular components involved in the release of drugs within a cell had been under debate for several years, Low said.

"This is the definitive statement on how drugs are released within a cell," he said. "We will use this knowledge to develop better receptor-targeted drug therapies to treat cancer and other diseases."

Low and Yang worked with scientists from the Department of Chemistry, Weldon School of Biomedical Engineering and Endocyte, and used facilities at the Oncological Sciences Center, part of the Purdue Cancer Center, and Bindley Bioscience Center at Purdue's Discovery Park.

Endocyte Inc. develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte has three compounds in Food and Drug Administration-regulated clinical trials: EC20, a targeted diagnostic agent that is in Phase II studies; EC17, a targeted-hapten therapy that is in Phase I studies; and EC145, a targeted cytotoxic agent that is in phase I studies. Endocyte has licensed its vitamin-targeting technology to Bristol-Myers Squibb to target Bristol-Myers Squibb's proprietary epothilone cancer chemotherapeutic agents.

Writer: Elizabeth K. Gardner, (765) 494-2081, ekgardner@purdue.edu
Sources: Philip S. Low, (765) 494-5273, plow@purdue.edu
Jun Yang, yangjun@purdue.edu
Purdue News Service: (765) 494-2096

Elizabeth K. Gardner | EurekAlert!
Further information:
http://www.purdue.edu

Further reports about: Disease Endocyte Target Yang delivery disulfide folic pathologic receptor

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>