Plant viruses are a new addition to the long list of types of nanoparticles being investigated as next generation nanotech cancer therapies. From North Carolina State University, via AAAS EurekAlert “Nanoparticle ‘smart bomb’ targets drug delivery to cancer cells“:
Researchers at North Carolina State University have successfully modified a common plant virus to deliver drugs only to specific cells inside the human body, without affecting surrounding tissue. These tiny “smart bombs” – each one thousands of times smaller than the width of a human hair – could lead to more effective chemotherapy treatments with greatly reduced, or even eliminated, side effects.
Drs. Stefan Franzen, professor of chemistry, and Steven Lommel, professor of plant pathology and genetics, collaborated on the project, utilizing the special properties of a fairly common and non-toxic plant virus as a means to convey drugs to the target cells.
The researchers say that the virus is appealing in both its ability to survive outside of a plant host and its built-in “cargo space” of 17 nanometers, which can be used to carry chemotherapy drugs directly to tumor cells. The researchers deploy the virus by attaching small proteins, called signal peptides, to its exterior that cause the virus to “seek out” particular cells, such as cancer cells. Those same signal peptides serve as “passwords” that allow the virus to enter the cancer cell, where it releases its cargo.
“We had tried a number of different nanoparticles as cell-targeting vectors,” Franzen says. “The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo.”
Calcium is the key to keeping the virus’ cargo enclosed. When the virus is in the bloodstream, calcium is also abundant. Inside individual cells, however, calcium levels are much lower, which allows the virus to open, delivering the cancer drugs only to the targeted cells.
“Another factor that makes the virus unique is the toughness of its shell,” Lommel says. “When the virus is in a closed state, nothing will leak out of the interior, and when it does open, it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug’s efficacy.”
The researchers believe that their method will alleviate the side effects of common chemotherapy treatments, while maximizing the effectiveness of the treatment.
Nanoparticles can be stabilized and targeted to specific cells (such as cancer cells) by attachment of specific proteins to the nanoparticles. How well those proteins stabilize and target the nanoparticle depends in part on how well the structure of the protein-nanoparticle complex is controlled. Viruses that lack a lipid envelope (that is, they consist of a genome surrounded by a protein capsid and other protein structures) provide a molecularly precise container of known structure and organization to which targeting molecules can be attached.
A 2007 Journal of the American Cancer Society paper (324 KB PDF,abstract) reports encapsidation of various nanoparticles up to 17 nm in diameter by the 36-nm diameter Red Clover Necrotic Mosaic Virus (RCNMV). This plant virus has a genome consisting of two single strand RNA molecules. The two genomic RNA molecules form a complex that binds the viral capsid protein and initiates the assembly of the virion. A small RNA molecule that mimics the site on the second genomic RNA required to initiate virion assembly can be tethered to various nanoparticles and then serve to initiate virion assembly, forming uniform virus-like particles about 33 nm in diameter—slightly smaller than the native virus particles—that encapsidate the nanoparticle within the protein shell. The relatively small size of the virus-like particles is an advantage because particles in the 30-nm range can be delivered directly to the cell nucleus via the nuclear pore complex. The virus-like particles are also sturdy enough to facilitate purification.