Story URL: http://news.medill.northwestern.edu/chicago/news.aspx?id=116321
Story Retrieval Date: 11/21/2014 6:00:59 PM CST
In cancer treatment, it’s all about search and destroy – search out and destroy cancer cells while leaving healthy tissue unharmed.
A group of PhD candidates at Northwestern University are making the search far more precise with nanotechnology. The students are customizing nanoconjugates – submicroscopic titanium dioxide (TiO2) particles attached to biological molecules. Such conjugates can be designed to carry specific cancer treatments and then bind only to harmful cells that need to be detected and destroyed.
Hans Arora, Eric Brown and K. Ted Thurn presented their findings on using nanoconjugates to target cancer cells at the 175th annual American Association for the Advancement of Science, held in Chicago this weekend. The research is at the cellular, or test tube, stage and could take years to develop for actual treatment.
Arora’s work focuses on attaching Doxorubicin, one of the most widely used therapeutic chemical agents to treat cancer, to a nanoparticle as a way of possibly stealthily getting the Doxorubicin into the cell.
“Many cancers are resistant to Doxorubicin. As with many drugs, you run into problems of resistance,” Arora said. “Once [a nanoconjugate treatment is] in the cell, then it can’t be kicked back out again because it’s attached to a molecule.”
The nanopackaging and binding capacity of the nanoconjugates allows the chemical to pass across the cell membrane.
Arora, who is also pursuing a medical degree, is experimenting on ovarian cancer cells, although Doxorubicin-TiO2 nanoconjugates can be applied to many different cancers.
“It’s a cross between biology and chemistry,” Arora said.
Thurn’s work focuses on investigating the ability of nanoconjugates to undergo endocytosis – the process by which cells absorb materials – to transfer cancer medications directly to targeted cells.
“If we’re using nanoparticles as a potential nanomedicine, one of the things you really need to understand at a very basic level is how nanoparticles interact with cells,” Thurn said.
By understanding how the endocytosis of nanoconjugates works, scientists can attach nanoconjugates with dyes to study ways to localize special parts of cells. By using fluorescent dyes, scientists can find where the nanoconjugate latched on in the cell, making sure they attached to the correct cellular structures.
Scientists also can excite the cell and get it to emit a unique fluorescent by shooting x-rays at it. This way, they can see the concentration of various elements within the cell, confirming the location of the nanoconjugates.
“If we can understand how cancer cells take up these particles, we can target [the cancer] while not targeting the regular, normal cells,” Thurn said.
Brown’s research focuses on imaging breast cancer cells and destroying them. He targets cancer by attaching nanoparticles to peptide nucleic acids, or PNAs – artificially synthesized sequences of DNA that can bind to their natural and complementary DNA sequences within a cell. Brown said the PNA-TiO2 nanoconjugate should be able to recognize the cancer DNA and cleave it, killing it off while leaving healthy cells alone.
“We were worried that certain enzymes in the cell would attack the DNA-TiO2 nanoconjugate and destroy it,” Brown said. “If you put a PNA-TiO2 nanoconjugate into a cell, since it’s synthetic, the enzymes in the cell won’t recognize it so it won’t be able to degrade it.”
Because the backbone of the PNA Brown used is neutrally charged, it binds to the cancer DNA with higher affinity than traditional DNA, since DNA is negatively charged. The PNA-TiO2 nanoconjugate also retains hydrogen bonds, which are critical for the PNA-TiO2 nanoconjugate to bond with other DNA strands.
The problem with chemotherapy and radiation now is that it usually destroys many healthy cells as well as harms the patient. Brown’s technique would hopefully someday help cancer patients suffer less during treatment, as the technique would be more effective.
Similar to Thurn’s research, by using a titanium dioxide nanoparticle with a red dye and attaching it to a strand of the PNA, the nanoconjugate will not only target the harmful DNA, but also provide a way for scientists to see where the cancer is located. Eventually, scientists and doctors could use this technology in conjunction with MRI scans so the cancer can be located more easily.
Although such treatments won’t be available yet, the team hopes their research will be combined to create an ultimate nanoconjugate that could detect cancer early, destroy it before it spreads and leave the rest of the body unharmed.
“The earlier you detect it, the higher chance someone has to survive,” Brown said.
The students are in the Integrated Graduate Program in Life Sciences and working under the direction of Dr. Gayle Woloschak, who is in the process of establishing nanotechnology collaborations in Egypt.