Molecular Hypodermic Needles
Introducing active pharmaceutical ingredients into the body is not difficult, but introducing them into cells in a targeted manner can be problematic. If pharmaceuticals are not taken up by cells to a sufficient extent, a suitable transporter must be found. A Franco-Italian research team successfully tried carbon nanotubes.
"They can pierce cell membranes like tiny needles," explains Alberto Bianco, "without damaging the cell." We are talking about carbon nanotubes – long, thin nano-scale tubes consisting of one or more layers of carbon atoms arranged like graphite. If proteins or nucleic acids are attached, they simply take them with them when they pass through the membrane.
Bianco and a team of scientists from the French research center CNRS in Strasbourg and the University of Trieste wanted to test whether this concept could also be extended to small active molecules such as antibiotics or cancer therapeutics. They found the idea of connecting not just one, but two different "passengers" particularly attractive. In this way, for example, combination therapies with different active substances could be carried out or the uptake of the active substance could be monitored using a marker.
Linking two different molecules to carbon nanotubes in a targeted, controlled and completely independent manner requires a sophisticated strategy. To do this, the researchers created two different types of "anchor points" on the tips and on the side walls of the tubes, which are provided with a kind of "protective caps". Then they could cleave off the first type of cap and attach molecule type 1, and then remove the second type and attach molecule type 2. The researchers loaded the tubes with amphotericin B, an antifungal agent, and a fluorescent dye.
By being coupled to the tubes, the antimycotic lost its otherwise typical toxic side effects. At the same time, its effectiveness against fungi has been increased. One reason could be the increased water solubility, and the active ingredient could no longer clump together. "Our approach could help broaden the use of amphotericin B against chronic fungal infections," Bianco hopes.
Carbon nanotubes, which are provided with an active ingredient and a "signpost" as passengers, also seem particularly attractive. The guide should then specifically recognize certain cell types, such as tumor cells, and guide the transporter there so that these cells preferentially absorb the active ingredient. © Angewandte Chemie