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 Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>