Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

DNA molecules used to assemble nanoparticles

24.01.2005


Dendrimer complex docking on cellular folate receptors. Image: Michigan Center for Biologic Nanotechnology


University of Michigan researchers have developed a faster, more efficient way to produce a wide variety of nanoparticle drug delivery systems, using DNA molecules to bind the particles together.

Nanometer-scaled dendrimers can be assembled in many configurations by using attached lengths of single-stranded DNA molecules, which naturally bind to other DNA strands in a highly specific fashion. "With this approach, you can target a wide variety of molecules---drugs, contrast agents---to almost any cell," said Dr. James R. Baker Jr., the Ruth Dow Doan Professor of Nanotechnology and director of the Center for Biologic Nanotechnology at U-M. Nanoparticle complexes can be specifically targeted to cancer cells and are small enough to enter a diseased cell, either killing it from within or sending out a signal to identify it. But making the particles is notoriously difficult and time-consuming.

The nanoparticle system used by Baker’s lab is based on dendrimers, star-like synthetic polymers that can carry a vast array of molecules on the ends of their arms. It is possible to build a single dendrimer carrying many different kinds of molecules such as contrast agents and drugs, but the synthesis process is long and difficult, requiring months for each new molecule added to the dendrimer in sequential steps. And the yield of useful particles drops with each successive step of synthesis.



For a paper published Jan. 21 in the journal Chemistry and Biology, U-M Biomedical Engineering graduate student Youngseon Choi built nanoparticle clusters of two different functional dendrimers, one designed for imaging and the other for targeting cancer cells. Each of the dendrimers also carried a single-stranded, non-coding DNA synthesized by Choi.

In a solution of two different kinds of single dendrimers, these dangling lengths of DNA, typically 34-66 bases long, found complementary sequences on other dendrimers and knitted together, forming barbell shaped two-dendrimer complexes with folate on one end and fluorescence on the other end. Folate receptors are over-expressed on the surface of cancer cells, so these dendrimer clusters would tend to flock to the diseased cells. The other end of the complex carries a fluorescent protein so that the researchers can track their movement.

A series of experiments using cell sorters, 3-D microscopes and other tools verified that these dendrimers hit their targets, were admitted into the cells and gave off their signaling light. The self-assembled dendrimer clusters were shown to be well formed and functional. "This is the proof-of-concept experiment," Choi said. But now that the assembly system has been worked out, other forms of dendrimer clusters are in the works. "If you wanted to make a therapeutic that targeted five drugs to five different cells, it would be 25 synthesis steps the traditional way," Baker said. At two to three months per synthesis, and a significant loss of yield for each step, that approach just wouldn’t be practical.

Instead, the Baker group will create a library of single-functional dendrimers that can be synthesized in parallel, rather than sequentially, and then linked together in many different combinations with the DNA strands. "So it’s like having a shelf full of Tinker Toys," Baker said.

An array of single-functional dendrimers, such as targets, drugs, and contrast agents, and the ability to link them together quickly and easily in many different ways would enable a clinic to offer 25 different "flavors" of dendrimer with only ten synthesis steps, Baker said.

Baker foresees a nanoparticle cluster in which a single dendrimer carries three single-strands of DNA, each with a sequence specific to the DNA attached to other kinds of dendrimers. Put into solution with these other tinker toys, the molecule would self-assemble into a four-dendrimer complex carrying one drug, one target, and one fluorescent.

Karl Leif Bates | EurekAlert!
Further information:
http://nano.med.umich.edu
http://lifesciences.umich.edu
http://www.chembiol.com

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

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

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>