09 Jan 2024
Rupture induced by mechanical action under near-IR light could offer treatment and therapy.Rice University has developed a way to destroy malignant cells, by having them vibrate strongly under near-IR illumination.
Published in Nature Chemistry, the research could open new routes to treatments or therapies for cancer using mechanical forces at the molecular scale.
The work builds on previous studies in the Rice lab of James Tour into nanoscale compounds bearing light-activated paddle-shaped chains of atoms, that spin continually in the same direction when under visible-light illumination. This can be used to drill through the outer membrane of infectious bacteria and treatment-resistant fungi.
Such a drilling approach is an alternative to other classes of molecular motors developed by Ben Feringa and recognized by the award of 2016's Nobel Prize in Chemistry, developed to exploit the way that light caused a photochemical isomerization around a molecule's double bond and changed its helicity. Cyclically inducing and relaxing this change produced a rotation of the molecule.
The principle behind the new Rice experiments is to attach aminocyanine molecules, a class of fluorescent synthetic dyes, to the target cells. These have previously been used for straightforward medical imaging by attaching them to the fatty outer lining of cells, but the Rice team investigated what happened when the dyes were instead activated as plasmons by the action of near-IR light.
Shake not bake: vibration not thermal action
"These molecules are simple dyes that people have been using for a long time,” commented Rice's Ciceron Ayala-Orozco. "Due to their structure and chemical properties, the nuclei of these molecules can oscillate in sync when exposed to the right stimulus."
This vibration creates a distinct type of molecular mechanical action that the Rice group terms vibronic-driven action (VDA), in which molecular plasmons created by near-IR light have a near-symmetrical structure with an arm on one side that helps anchor the molecule to the cell membrane, according to the project.
Since the VDA effect causes whole-molecule vibration in the target dyes, the project has termed them "molecular jackhammers," and investigated whether this action could cause enough physical damage to cancer cells to kill them off. If so, this would be distinctly different to photodynamic or photothermal therapy, as it would not involve thermal killing of the cells or be affected by reactive oxygen species on the cell membranes.
In trials the team found that "sub-picosecond concerted whole-molecule vibrations of VDA-induced mechanical disruption can be achieved using very low concentrations of aminocyanines or low doses of light, resulting in complete eradication of human melanoma cells in vitro," according to the group's published paper.
Since near-IR can penetrate more deeply into tissues than the visible light used for the earlier nanodrill studies, the VDA principle marks a significant advance towards applying the principles of molecular mechanical action to useful clinical operations.
"This is the first time a molecular plasmon is utilized in this way to excite the whole molecule and to actually produce mechanical action used to achieve a particular goal, in this case tearing apart cancer cells' membrane," said Ciceron Ayala-Orozco. "This study is about a different way to treat cancer using mechanical forces at the molecular scale."