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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>