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)

A depiction of what the silicon nanowires look like. This array of nanowire detectors is able to detect single proteins in the bloodstream. Each nanowire corresponds to a different antibody. Credit: Vista Therapeutics

I can see it now. Season 43 of House M.D. House asks his team of fellows to determine the concentration of a certain protein in a patient’s bloodstream. Instead of taking multiple blood samples and performing several tests, including purifying the samples, marking the designated proteins, and using imaging technology to check for the labeled proteins, the fellows simply use special nanowire sensors to accomplish in five minutes what originally took 90 minutes. Although House may not be around for 43 seasons, the scene just described may be commonplace in hospitals all over the world. This ground-breaking technology is currently being researched by Vista Therapeutics, as they aim to provide the “ultimate sensitivity” with this new product.

Here is a description provided by the MIT Technology Review:

To make the detectors, Vista Therapeutics has licensed nanowire sensing technologies developed by Harvard University chemist Charles Lieber. Silicon nanowires, semiconducting wires as thin as two nanometers, have what Lieber calls the “ultimate sensitivity,” even with completely unprocessed samples such as blood. When a single protein binds to an antibody along the wire, the current flowing through the wire changes. Arrays of hundreds of nanowires, each designed to detect a different molecule in the same sample, can be arranged on tiny, inexpensive chips. The changes can be monitored continuously as molecules bind and unbind, making it possible to detect subtle trends over time, without requiring multiple blood draws.

The standard protein-detection technique, ELISA, is very sensitive but, Farr says, takes 90 minutes to perform. It starts with a blood draw that must be extensively processed–first to purify the proteins, then to label them with fluorescent dyes–and then tested with expensive imaging equipment in a hospital lab. “ELISA is a powerful technology for one-time measurements,” says Farr, “but there’s no existing technology for continuous biomarker measurement.”

With the ability to perform extremely precise, continuous monitoring of unprocessed blood samples, who knows what the future holds in store for nanowire detectors. You can be sure that I’ll be waiting for its debut on House.