Tiny hitchhikers attack cancer cells: Gold nanostars first to deliver drug directly to cancer cell nucleus

Apr 05, 2012

Nanotechnology offers powerful new possibilities for targeted cancer therapies, but the design challenges are many. Northwestern University scientists now are the first to develop a simple but specialized nanoparticle that can deliver a drug directly to a cancer cell's nucleus -- an important feature for effective treatment.

They also are the first to directly image at nanoscale dimensions how interact with a cancer cell's nucleus.

"Our drug-loaded nanostars are tiny hitchhikers," said Teri W. Odom, who led the study of human cervical and . "They are attracted to a protein on the cancer cell's surface that conveniently shuttles the nanostars to the cell's nucleus. Then, on the nucleus' doorstep, the nanostars release the drug, which continues into the nucleus to do its work."

Odom is the Board of Lady Managers of the Columbian Exposition Professor of Chemistry in the Weinberg College of Arts and Sciences and a professor of materials science and engineering in the McCormick School of Engineering and Applied Science.

Using , Odom and her team found their drug-loaded nanoparticles dramatically change the shape of the cancer . What begins as a nice, smooth ellipsoid becomes an uneven shape with deep folds. They also discovered that this change in shape after drug release was connected to cells dying and the becoming less viable -- both positive outcomes when dealing with .

The results are published in the journal ACS Nano.

Since this initial research, the researchers have gone on to study effects of the drug-loaded gold nanostars on 12 other human cancer cell lines. The effect was much the same. "All cancer cells seem to respond similarly," Odom said. "This suggests that the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery."

The nanoparticle is simple and cleverly designed. It is made of gold and shaped much like a star, with five to 10 points. (A nanostar is approximately 25 nanometers wide.) The large surface area allows the researchers to load a high concentration of drug molecules onto the nanostar. Less drug would be needed than current therapeutic approaches using free molecules because the drug is stabilized on the surface of the nanoparticle.

The drug used in the study is a single-stranded DNA aptamer called AS1411. Approximately 1,000 of these strands are attached to each nanostar's surface.

The DNA aptamer serves two functions: it is attracted to and binds to nucleolin, a protein overexpressed in cancer cells and found on the cell surface (as well as within the cell). And when released from the nanostar, the DNA aptamer also acts as the drug itself.

Bound to the nucleolin, the drug-loaded gold nanostars take advantage of the protein's role as a shuttle within the cell and hitchhike their way to the cell nucleus. The researchers then direct ultrafast pulses of light -- similar to that used in LASIK surgery -- at the cells. The pulsed light cleaves the bond attachments between the gold surface and the thiolated DNA aptamers, which then can enter the nucleus.

In addition to allowing a large amount of drug to be loaded, the nanostar's shape also helps concentrate the light at the points, facilitating drug release in those areas. Drug release from nanoparticles is a difficult problem, Odom said, but with the gold nanostars the release occurs easily.

That the gold nanostar can deliver the without needing to pass through the nuclear membrane means the nanoparticle is not required to be a certain size, offering design flexibility. Also, the nanostars are made using a biocompatible synthesis, which is unusual for nanoparticles.

Odom envisions the drug-delivery method, once optimized, could be particularly useful in cases where tumors are fairly close to the skin's surface, such as skin and some breast cancers. (The light source would be external to the body.) Surgeons removing cancerous tumors also might find the gold nanostars useful for eradicating any stray cancer cells in surrounding tissue.

Explore further: Cloaked DNA nanodevices survive pilot mission

More information: "Direct Observation of Nanoparticle-Cancer Cell Nucleus Interactions." pubs.acs.org/doi/abs/10.1021/nn300296p

Related Stories

Overcoming cancer drug resistance with nanoparticles

Jan 20, 2012

One of the ways in which cancer cells evade anticancer therapy is by producing a protein that pumps drugs out of the cell before these compounds can exert their cell-killing effects. A research team at Northwestern University ...

Gold nanoparticles for controlled drug delivery

Dec 30, 2008

(PhysOrg.com) -- Using tiny gold particles and infrared light, MIT researchers have developed a drug-delivery system that allows multiple drugs to be released in a controlled fashion.

Using Gold Nanoparticles to Hit Cancer Where It Hurts

Feb 15, 2010

(PhysOrg.com) -- Taking gold nanoparticles to the cancer cell and hitting them with a laser has been shown to be a promising tool in fighting cancer, but what about cancers that occur in places where a laser light can’t ...

Attacking cancer cells with nanoparticles

Oct 25, 2011

(PhysOrg.com) -- About every three days, Colleen Alexander, a chemistry graduate student, feeds cells that cause a deadly type of brain cancer. It’s a ritual that involves assessing the health of the ...

Gold used as safe driver of cancer drug

Mar 21, 2012

(PhysOrg.com) -- Gold nanoparticles can be used as delivery vehicles for platinum anticancer drugs, improving targeting and uptake into cells, according to research published in this month's edition of the ...

Recommended for you

Cloaked DNA nanodevices survive pilot mission

Apr 22, 2014

It's a familiar trope in science fiction: In enemy territory, activate your cloaking device. And real-world viruses use similar tactics to make themselves invisible to the immune system. Now scientists at ...

Innovative strategy to facilitate organ repair

Apr 18, 2014

A significant breakthrough could revolutionize surgical practice and regenerative medicine. A team led by Ludwik Leibler from the Laboratoire Matière Molle et Chimie (CNRS/ESPCI Paris Tech) and Didier Letourneur ...

Physicists create new nanoparticle for cancer therapy

Apr 16, 2014

A University of Texas at Arlington physicist working to create a luminescent nanoparticle to use in security-related radiation detection may have instead happened upon an advance in photodynamic cancer therapy.

User comments : 0

More news stories