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 New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | 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: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>