Bench Press

Today modern medicine provides patients with numerous drugs for an enormous number of health issues. For example, getting relief from a headache can be as simple as popping open a bottle of aspirin and swallowing a couple pills. While to the patient the delivery of the drug begins and ends with swallowing those two pills with a glass of water, to the scientists working on the drug that’s simply the beginning of numerous steps that hopefully result in a drug surviving the trip through the body to it’s intended target and doing it’s job.

Drugs are therefore designed not just to solve a problem but to survive the human body’s natural mechanisms. The gauntlet of obstacles that a drug faces upon entry into the body is a major reason why many researchers continue to look into innovative techniques for delivering pharmaceuticals.

That’s where research being conducted by Drs. Stefan Franzen and Steve Lommel comes in. Working with the red clover necrotic mosaic virus (RCNMV), Drs. Franzen and Lommel have developed a potential revolutionary drug delivery platform.

Figure 1. Production of Drug Vector

Drs. Franzen and Lommel take advantage of a 17 nanometer space within the 38 nanometer icosahedral capsid of RCNMV in order to store therapeutics. The RCNMV infused with the drugs could then be used to deliver the drugs in a cell specific manner with the addition of targeting peptides.

The preparation of the drug carrying virus is elegant in it’s simplicity and produces a robust delivery mechanism (See Fig 1). First RCNMV is treated with EDTA to open pores in the capsid. Next therapeutics are infused through these open pores. The pores are then sealed with Ca²⁺ which is key in releasing the drug later upon viral entry to the cell. The prepared virus can then be purified via dialysis followed by adding target specific peptides.

The elegance of using Ca²⁺ to seal the pores lies in the fact that the human bloodstream is abundant in calcium. Inside cells, calcium levels are much lower, allowing the pores to open up thereby delivering the infused therapeutics only when the target cell has been entered.

In vitro work with Doxorubicin, a cancer drug, infused RCNMV shows promising results (see Fig 2.) promoting apoptosis only when provided with targeting peptides allowing the drug to be delivered to the interior of cells.

Figure 2. Delivery of Doxorubicin RCNMV to HeLa cells

A potential application of this research is in cancer treatment. Current chemotherapy treatments often result in dramatic side effects as the drugs do not distinguish between diseased and healthy cells. While these results are probably still years from resulting in a commercial therapy it provides hope that in the near future doctors will be able to prescribe chemotherapy treatments with dramatically reduced side effects thanks to target specific delivery of the drugs.

(Sources: NCSU – results. , NCSU News , Franzen Presentation – Plant Virus Nanotechnology)

Part of why I became so interested in science as a kid (apart from watching Bill Nye) was seeing the application of science in medicine. Seeing the development of new medicinal techniques thanks to innovative research made a lasting impression on me. I guess that’s why a level of childhood excitement tends to pop up when I read about things like new imaging technology and future surgical innovations.

A schematic of Dr. King's cancer filtering concept. E-selectin attracts the cancer cells thereby exposing them to TRAIL as they "roll" along the device wall. This triggers the cancer cell's death. Image: Kuldeep Rana

Once again I felt that childhood excitement popping up as I read about a new device being developed by Dr. Michael King and his group at Cornell designed to someday remove cancerous cells from a patient’s bloodstream. King’s device takes advantage of a well studied mechanism of our immune system which is the recruitment of white blood cells to blood vessel walls with adhesion molecules known as selectins. Since selectins recruit cells based on specific carbohydrates Dr. King realized that this adhesive property could be utilized for slowing down cancer cells in order to target and destroy them.

After slowing down the cancer cells to a “roll” the cells can then be exposed to a protein called TRAIL (Tumor Necrosis Factor Related Apoptosis-Inducing Ligand) resulting in the release and then the apoptotic death of the cancer cells. This makes King’s device more than a simple sieve as he explains, “It’s a little more sophisticated than just filtering the blood, because we’re not just accumulating cancer cells on the surface”.

King’s device is impressive in it’s simplicity and tests of the device’s efficacy appear promising.

King’s research showed that the device can capture and kill about 30 percent of cancer cells flowing past it a single time, with the potential to kill more in the closed-loop system of the body. Used in combination with traditional cancer therapies, King said, the device could remove a significant proportion of metastatic cells, “and give the body a fighting chance to remove the rest of them.”

The team also showed that a system in which the cancer cells “roll” over the target molecules – presenting their entire surface to the molecules – is four times more effective than a static setup in which the cells and proteins make contact at a single point.

Of course as excited as I am to see this type of work being done, as Dr. King points out moving his concept to the clinic may take many years. I’m looking forward to reading the paper in Biotechnology and Bioengineering and seeing what others will come up with from Dr. King’s work.