Molecular Jackhammers Eradicate Cancer Cells by Vibronic-Driven Action

Molecular Jackhammers Eradicate Cancer Cells by Vibronic-Driven Action: https://www.biorxiv.org/content/10.1101/2023.01.25.525400v1

Abstract

Through the actuation of vibronic modes in cell-membrane-associated aminocyanines, a new type of molecular mechanical action can be exploited to rapidly kill cells by necrosis. This is done using near-infrared light, a low energy source hitherto thought to be insufficient to permit molecular mechanical disruption of a cell membrane. Vibronic-driven action (VDA) is distinct from both photodynamic therapy and photothermal therapy in that the VDA mechanical effect on the cell membrane is not retarded by high doses of inhibitors of reactive oxygen species (ROS), and VDA does not itself induce an increase in the temperature of the media; it is also unaffected by cooling the media to 2 °C. The picosecond concerted whole-molecule-vibrations of VDA-induced mechanical disruption can be done with very low concentrations (500 nM) of the aminocyanines or low doses of light (12 Jcm-2, 80 mWcm-2 for 2.5 min) to cause in vitro necrotic cell death in >99% of human melanoma cells. The effect is also studied in vivo in murine B16-F10 and human A375 melanoma in mice, underscoring the high efficiency of this approach, achieving a survival rate of 60% at day 120, and 50% of the mice becoming tumor free. The molecules that destroy cell membranes through VDA are termed molecular jackhammers (MJH) because they undergo concerted whole-molecule vibrations. Different than traditional chemotherapy, it is unlikely that a cell could develop a resistance to molecular mechanical forces, thereby providing a new modality for inducing cancer cell death.

Note: From further down in the paper, "While UV and visible light have only hundreds of microns to 1 mm of light penetration
through human tissue (skin, muscle, fat), the NIR window of 650 nm to 900 nm, also known as
the optical therapeutic window, is ideally suited for in vivo applications because of minimal light
absorption by hemoglobin and water with significant penetration through human tissue reaching
~10 cm.5" They are using NIR light to drive 2-3 MHx unidirectional rotation in these molecular motors, which create "drilling action on cellular membranes develop holes in the cell, then blebbing
and death within seconds to minutes of activation."