Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New cancer drug delivery system is effective and reversible

10.08.2009
For cancer drug developers, finding an agent that kills tumor cells is only part of the equation. The drug must also spare healthy cells, and – ideally – its effects will be reversible, to cut short any potentially dangerous side effects.

University of Illinois researchers report that they have assembled a new cancer drug delivery system that, in cell culture, achieves all of the above. The findings appear this month in the journal Angewandte Chemie.

The team began with the knowledge that small, membrane-bound compartments, called liposomes, are useful as drug-delivery vehicles. When linked to molecules that target receptors on cancer cells, liposomes can enter and dump their cancer-killing contents into those cells.

Scientists have spent more than a decade trying to direct liposomes to specific cancer cells, with limited success. A common approach involves attaching an antibody to the liposome membrane. Ideally the antibody will bind to a cancer cell receptor so that it can deliver the liposome – and the cancer drug – into the cell.

Developing such antibodies is costly and time-consuming, however, and the process of attaching them to liposomes is difficult to control. Antibodies spur an immune response, requiring extra steps to create a useable therapeutic agent, and the ability of antibody-conjugated liposomes to bind to cancer cells can be inconsistent.

Some small molecules, such folate, a vitamin, also work as cancer cell targeting agents, but those now in use are not as good as antibodies at binding to cancer cells.

To solve the cell-targeting problem, the U. of I. team turned its attention to small molecules called aptamers.

"Aptamers are short strands of DNA or RNA; they are highly efficient binders, and are very easy to make, label and manipulate," said Zehui Cao, a postdoctoral researcher in the laboratory of chemistry professor Yi Lu, who led the study. Materials science and engineering professors Gerard Wong and Jianjun Cheng were co-principal investigators on the study with Lu. Graduate students Rong Tong (who is co-first author on the paper with Cao), Abhijit Mishra and Weichen Xu also worked on the study.

Lu's laboratory specializes in isolating aptamers that bind to specific molecules and converting them into effective sensors and diagnostic agents. His team used an aptamer that binds to nucleolin receptors, which are found in abundance on certain breast cancer cells. The researchers then developed an effective method for attaching the aptamer to a liposome loaded with cisplatin, a drug that effectively kills cancer cells but has troublesome side effects when administered intravenously.

Tests in cells grown in the lab yielded promising results. Four days after they exposed the cells to the new drug-delivery system, 59.5 percent of the breast cancer cells had died, while less than 12 percent of breast cancer cells treated with cisplatin alone had died.

"By labeling a liposome that contains cisplatin with a cancer cell-specific aptamer, we have shown delivery of the drugs to cancer cells without significant damage to regular cells," Lu said, "making it possible to maximize the drug potency while minimizing its side effects."

This approach "integrates the advantages of small molecules and antibodies," said Cheng, who helped pioneer the use of aptamers as targeting molecules for drug delivery. "This is the first study to integrate the aptamers and the liposome."

Another advantage of using aptamers as targeting agents is that they are easily disabled. They readily bind to complementary DNA, which prevents them from interacting with cell receptors.

The new approach will be useful for many applications, Wong said. "What we're really doing here is coming up with a general toolbox to deal with a broad range of cancers."

"You can change aptamers to target a different type of cancer, you can change the therapeutic molecules to fight cancer or other diseases, and you can reverse the dose," Cheng said. "That's a lot of tools in the toolbox. It has great potential."

The collaboration between materials scientists and chemists was made possible by administrative structures at the U. of I. that foster such partnerships, Wong said. The work was supported by a National Science Foundation (NSF) Nanoscale Science and Engineering Center grant, the NSF Career Program, and the Siteman Center for Cancer Nanotechnology Excellence (SCCNE, Washington University) – Center for Nanoscale Science and Technology (CNST, UIUC).

The paper: "Reversible Cell-Specific Drug Delivery With Aptamer-Functionalized Liposomes," appeared July 21, 2009, in Angewandte Chemie. The authors: Zehui Cao, Rong Tong, Abhijit Mishra, Weichen Xu, Gerard C L Wong, Jianjun Cheng, and Yi Lu, of the University of Illinois. Full text of the article is available online: http://highwire.stanford.edu/cgi/medline/pmid;19623590.

Diana Yates | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>