Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researcher lights the way to better drug delivery

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,
Sources: Philip S. Low, (765) 494-5273,
Jun Yang,
Purdue News Service: (765) 494-2096

Elizabeth K. Gardner | EurekAlert!
Further information:

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

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>