Researchers in the US and the UK have developed a completely new technique to open cell membranes using photosensitive molecular machines. The devices, which drill their way through cellular lipid bilayers when exposed to light, can also destroy cells within minutes by disrupting the cell membrane. They might be used to deliver therapeutic drug payloads into targeted diseased cells, or to kill such cells.
A prostate cell under attack
“Last year’s Nobel Prize in Chemistry was awarded to Bernard Feringa for his work on the design and synthesis of molecular machines, and since then many have asked, ‘what are these machines good for?’ Our technique proves how useful these devices can be,” team leader James Tour of Rice University in Houston, Texas, tells nanotechweb.org. “In our work, we have something that no other entity so small has ever done before. And the effect can be targeted to specific cells – such as cancer cells, for example.”
The new molecular machines, which are about a nanometre wide, have a rotor head and a stator. When activated with 355–365 nm wavelength ultraviolet light, the devices rotate at 2–3 megahertz (two-to-three million times per second). “When attached to a cell membrane, they displace membrane molecules in their path, and thus open up a hole in the cell,” explains Tour. “When the nanomachines open holes in the membrane, exogenous drugs that have been added to them can follow in behind them.”
Nanomachine incorporates a static body and a light-activated rotor
The machines (with their drug payload) can be designed to target a cell’s lipid bilayer membrane and then tunnel through it, or they can be designed to simply disrupt the 8–10 nm-wide membrane, thereby killing the cell, he adds. They can also be functionalized to be soluble and labelled with florescence markers so they can be tracked.
Co-workers at North Carolina University, led by Gufeng Wang, helped the Rice team to make different kinds of motors, including those of different sizes and carrying various payloads. The researchers tracked the motors using fluorescent dyes, and observed the signal from the dye gradually fade away as the motor pierced the lipid membrane. Their colleagues at Durham University in the UK, led by Robert Pal, tested out these motors on live cells, including human prostate cancer cells. The experiments showed that the machines killed the cells with one to three minutes of being activated with UV light.
Motorized molecules target diseased cells
The researchers hope that they will eventually be able to activate the machines using two-photon absorption, near-infrared light or radiofrequencies. This would make the technique more suitable for real-world in-vivo treatment. Indeed, they are already performing experiments on microorganisms and small fish to investigate how efficient their technique is. “The hope is to move these swiftly to rodents,” says Tour.
The technique is particularly suited to targeting or destroying a specific cell type, he continues. “In many other photodynamic therapies, there is always the problem of surrounding healthy cells being targeted at the same time, but since we can irradiate our motors specifically in the region desired, only motors in the path of the irradiating light will be activated to target or kill a cell. Off-target motors will not be in the light’s path so will not be activated. It’s like having a dual assurance that only the targeted cells will be destroyed or treated.”