Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

DNA molecules used to assemble nanoparticles

16.03.2005


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.

Nancy Ross-Flanigan | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>