Viral protein takes drugs into cells
that can transport active drugs into the interior of cells by an
intrinsic, active mechanism.
The hope is that the technology could be used both to improve the take-up drugs by cells, increasing the efficacy of treatment while reducing the dose that has to be delivered and the potential for side effects.
The company, called responsif, has developed a technique that makes use of artificial structures from a virus, called a capsoid, that can attach onto cells. This capsoid can be modified to carry an active drug.
To make the capsoid, the responsif scientists used a viral coat protein found on the surface of the murine polyoma virus, while the anchor protein was taken from the inner part of the viral capsoid. They then tested the delivery mechanism by attaching the anticancer drug methotrexate and a fluorescent marker molecule to the anchor protein.
When exposed to light of a certain wavelength, the marker protein emits a green fluorescence, and this allowed the scientists to demonstrate that, under suitable conditions, complete protein capsoids will form in the reaction mixture and envelope active drug substance.
The resulting viral capsules each contained up to 462 methotrexate molecules - or 64 polypeptides - on average. Importantly, they also showed regular morphology and stability for several months.
Furthermore, when the capsules were brought into contact with living cells, the cells actively take up the capsules. As proof, the researchers presented microscopic photos showing the fluorescent green capsoids inside the cells.
And when polyoma capsules containing methotrexate molecules were mixed with leukaemia cells, they lost their capability for cell division, providing preliminary evidence that the transport system could be used therapeutically.
Vaccination approach
The scientists said that the system offers an effective mechanism for delivering active substances to the cell. Their ultimate aim, however, is to develop a cancer therapy in which the body's own endogenous defense system plays a decisive role.
In the opinion of the researchers, the tumour antigens enclosed in the responsif capsoids could be used to stimulate the immune defence system, which at present does not recognise tumour antigens efficiently enough. The therapeutic efficacy of recombinant capsoids against cancer cells has already been demonstrated successfully by responsif in animal experiments.
A paper on the technology has been published in the online version of the Journal of Biological Chemistry.
