This is the first method that practically forces cancer cells to incorporate a cytostatic drug, explains team leader Andrei Sommer. Most existing methods rely on cells to uptake drugs into their interior – something that can be done via passive diffusion across the bilayer lipid structure of the cell membrane, for example, or by diffusion involving transport proteins anchored in the cell membrane. However, such chemotherapy is often hampered by an effect called multi-drug resistance in which transmembrane "efflux" systems simply push out the drug. Researchers are currently trying to overcome this problem and are now looking into chemical and biochemical methods that primarily target the cell membrane rather than the interior of the cell itself.

In contrast to these mainstream methods, Sommer's team is focusing on the volume of the cell. When irradiated with moderately intense (1000 W/m2) laser light with a wavelength of 670 nm, both the density and viscosity of intracellular water decrease, so expanding its volume (since density=mass/volume). Intracellular water exists at the interface between neighbouring hydrophilic surfaces, such as macromolecules and organelles in cells.

Sucking in drugs
The density and viscosity of such nanoscopic interfacial water layers are higher than that of "ordinary" bulk water and irradiating this water with laser light decreases its density – a phenomenon that is not seen for bulk water. When the laser is turned off, the interfacial water layers reorganize and a negative pressure builds up, causing the water between the cells to retract instantly. "This means that surrounding solutions (containing drug molecules) can then be literally sucked into the cell," Sommer told nanotechweb.org.

The Ulm team confirmed its technique by using green tea as a model drug for human cervical cancer cells. Green tea contains high concentrations of epigallocatechin gallate (EGCG), which is a potent tumour inhibitor. According to the researchers, the method might also be extended to a multitude of other anticancer drugs.

Pulsed light and its applications
Pulsed light is routinely used today in facial rejuvenation. It has also been found to increase cell numbers in vitro. Until now, however, scientists were unsure about how the laser light caused the effects seen. The new work shows that the light-cell pump mechanism helps in transporting molecules (be they nutrients or drugs) into cells.

Sommer and colleagues now intend to evaluate optimal laser pulse patterns and try out their technique in vivo in the future. They also say that their method might be used in conjunction with other chemotherapy techniques. EGCG as a drug – either applied topically or injected – in combination with red laser light could also be promising for treating skin cancers.

The work was published in Photomedicine and Laser Surgery.