Self-destroying ‘nanosubmarine’ could deliver drugs direct to tumours
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Dutch researchers have developed a nano-vessel capable of self-propelling itself to a tumour and spontaneously breaking apart to release an anti-tumour drug.
Nanosubmarines (or nanomotors) are tiny devices designed to navigate around the human body and perform specialised tasks, such as microsurgery or targeted drug delivery.
While the idea of miniature machines performing medical procedures within the body has existed in popular imagination for decades, developing a self-propelling nanomotor capable of controlled, targeted release is still a challenge for researchers.
Researchers at Radboud University in the Netherlands, however, have celebrated success in developing nanosubmarines which autonomously deliver and release drugs for cancerous cells, self-destructing in the process. These would combine a number of desirable qualities: self-propulsion, drug encapsulation and self-destruction.
The anti-tumour drug itself is concealed inside a protective shell of polyethylene glycol (PEG) and polystyrene, connected by a “bridge” of a disulphide bond. Once assembled, the structure is turned into an artificial red blood cell with the addition of an “engine”: platinum nanoparticles.
The platinum nanoparticles break down hydrogen peroxide – produced in high quantities by tumour cells – and this propels the vessel forward. Once the nanosubmarine has passed through the cell membrane, the drug can be released inside it.
The trigger for the drug release is a chemical signal (an oxidation-reduction (redox) reaction) in the presence of high concentrations of glutathione. Gluthathione is crucial in “[pressing] the door handle” to the nanosubmarine and releasing the drug.
This was stumbled upon by Professor Daniela Wilson – head of the Radboud systems chemistry department – and her team during attempts to identify a “door-opener” for their nanosubmarine. Gluthathione is a “redox molecule”: an antitoxidant. High levels of gluthathione are found inside tumour cells, the drug targets.
“The small glutathione can enter into the PEG shell of the nanomotor and then break down the redox-responsive disulphide bonds, resulting in cleavage of the outside PEG shell,” the researchers write.
Once these disulphide bonds are broken, glutathione causes disassembly of the membrane, opening the nanosubmarine and releasing the drug.
Using clusters of human cells in the laboratory, the researchers demonstrated that the nanomotors could navigate and disintegrate as hoped. In their Angewandte Chemie article, they describe the nanosubmarine as “promising for drug delivery applications in the future”.