Getting a class of fluorescent synthetic dyes used for medical imaging to embed in the membranes of cancer cells and vibrate rapidly induces necrosis.

With whole-molecule vibrations lasting for less than a picosecond, these vibrating aminocyanines can mess up how things work at low light levels or concentrations. With this “molecular jackhammer” technique, researchers from Rice University, the University of Texas MD Anderson Cancer Center, and Texas A&M University demonstrated the complete eradication of human melanoma cells in vitro. They achieved 50% tumor-free efficacy in mouse models for melanoma.

Given that a cell is unlikely to develop resistance to such molecular mechanical forces, molecular jackhammers offer an alternative method of inducing cancer cell death. This study demonstrates a unique mechanical action at the molecular scale to eradicate cells and possibly treat cells using adjuvants. 

The research article, “Molecular jackhammers eradicate cancer cells by vibronic-driven action,” was published in Nature Chemistry.

Researchers have been trying to use tools to kill cancer cells, such as unidirectional synthetic molecular motors (called Feringa motors) that drill holes in cell membranes, resulting in rapid necrotic death. This tactic works great in a dish, but many of the existing tools require light-based activation when it comes to whole animals. 

While UV and visible light penetrate only hundreds of micrometers to 1 mm through human tissue (skin, muscle, and fat), the near-infrared (NIR) window of 650–900 nm, also known as the optical therapeutic window, is ideally suited for in vivo applications owing to minimal light absorption by hemoglobin and water coupled with substantial penetration through human tissue reaching ~10 cm. Despite great efforts to tune the rotational frequency of molecular motors to higher wavelengths, one that can rotate at the NIR frequency has yet to be reported.

In this study, Ciceron Ayala-Orozco, PhD, a scientist at Rice University, and colleagues leveraged molecular jackhammering on cells induced by single-photon NIR light. They found that turning on the vibronic mode of aminocyanines connected to the cell membrane causes coordinated whole-molecule vibrations that quickly kill cells. Cyanine dyes have been used in photothermal and photodynamic therapies and are readily accepted in biological and medicinal studies.

The researchers are now identifying and synthesizing other small molecules that can accentuate this combination of features for cell binding and vibration-driven action. Different uses could include controlling which parts of enzymes are active, changing how protein channels work, or changing the structure or function of large biological assemblies that affect drugs.

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