September 3, 2013

Prof. Ulrich Wiesner Creates World’s Smallest Drug Delivery Particles

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Treating diseases such as cancer can be difficult for patients due to the toxicity of the medicines they must take. Prof. Ulrich Wiesner, materials science and engineering, has taken steps toward resolving this problem by creating the world’s smallest drug delivery particles.

Wiesner’s specialized particles, called Cornell dots, or C-dots, avoid the toxic  side effects caused by larger drug delivery particles because larger particles must be removed by the liver instead of the kidneys. According to Wiesner, particles cleared by the liver can take weeks or even months to clear from the body, while waste removal through the kidneys can reduce exposure to the toxic drugs to around six hours.

C-dots are under 10 nanometers in diameter, about 10,000 times smaller than the average thickness of a single strand of human hair, and can therefore be removed through the kidneys instead of the liver, Wiesner said.

According to Wiesner, C-dots have a silica shell that encapsulates dye molecules. The dye molecules make the particles fluoresce allowing them to also be used for imaging tumor sites during surgery to allow for a more precise removal of the tumor. According to Wiesner, current imaging techniques like MRI, CT and PET scans are expensive, and the size of the equipment prevents them from being used in the operation room.

To use C-dots for drug delivery, the team started by attaching the drug to the surface of the particle’s shell. But they encountered problems because the chemotherapeutic drugs are hydrophobic, water fearing, and tended to aggregate into larger particles in the body and go directly to the liver instead of the tumor site. This defeated the original purpose of the C-dots.

“This is when we hit upon this idea to generate particles as the first-generation C-dots but have a pore made in the core of the particle to tuck away the hydrophobic drug,” Wiesner said.

The second generation of C-dots are called mesoporous Cornell dots, or mC-dots, added a pore in the middle which gives them the additional capability of carrying drugs. Although the original synthesis  of these new particles took almost two years, Wiesner and Kai Ma grad can now produce the particles in one week.

Wiesner and his collaborators seek to use these mC-dots to both image and supply drugs to cancerous tumor sites.

To get the mC-dots to attack the tumor site, organic molecules like peptides or fractions of antibodies are attached onto the particles’ surface. These organic molecules can be tumor specific and tend to stick to the tumor surface or even locations within the tumor.

Some current chemotherapy drugs are taken orally. These drugs make their way to the tumor site after being diffused from the digestive system into the bloodstream. These drugs, however, can also diffuse to other parts of the body causing unwanted side effects. According to Wiesner, the advantage of using mC-dots as the drug deliverer would be that the mC-dots would either attack the tumor site or get excreted from the body with no major side effects.

Wiesner’s lab is currently in the process of verifying if the drugs can be introduced in the pore of the mC-dots. They are also checking for any differences in the behavior of these particles in the body due to the addition of the drugs.

Although this preliminary work with C-dots shows promise, Wiesner said there is a long way to go before the particles can be regularly used in cancer treatments.

Original Author: Srinitya Arasanipalai