Researchers have identified a new cancer treatment approach using molecules dubbed molecular jackhammers (MJHs), which are aminocyanines capable of mechanically disrupting cancer cell membranes through vibronic-driven action (VDA) when activated by near-infrared light.
Key Concept: Vibronic-Driven Action
VDA operates through subpicosecond whole-molecule vibrations of aminocyanines bound to cell membranes, initiated by targeted light exposure . This mechanical process rapidly induces necrosis in cells—unlike traditional photodynamic or photothermal therapies, it does not rely on reactive oxygen species (ROS) generation nor heat.
Experimental Findings
At concentrations as low as 500 nM, MJHs used in conjunction with low-dose near-infrared light (e.g., 12 J/cm², 80 mW/cm² for 2.5 minutes) completely eradicated human melanoma cells in vitro . The study also demonstrated 50% tumor-free efficacy in mouse melanoma models, suggesting promise for living organism applications.
Cellular Interaction
Confocal microscopy and flow cytometry reveal rapid and effective binding of MJHs to both external and internal cell membranes in human melanoma cells . However, membrane composition—such as the presence of acetic acid, which alters phospholipid protonation—can diminish MJH binding, reducing efficacy.
Selectivity and Safety Profile
Significantly, cell death via MJH activation is not influenced by ROS inhibitors or changes in temperature, underscoring the unique, non-chemical, non-thermal mechanical disruption. Comparative studies with strong photosensitizers like DiR show that high ROS production alone cannot match the efficacy of MJHs’ VDA for permeabilization and cell death.
Quantitative Cell Death Assays
Crystal violet and clonogenic assays further confirm the robust, concentration-dependent effect of MJHs: exposure to Cy7.5-amine plus light leads to complete eradication of cell colonies with very high statistical significance in all tested conditions .
Resistance Implications
Because the action mechanism is fundamentally mechanical—causing necrosis by physically disrupting the cell membrane—cancer cells are unlikely to develop resistance to MJH-induced VDA, a major advantage over therapies targeting biochemical pathways.
Practical and Ethical Aspects
Rice University holds intellectual property for MJH/VDA technology, with researchers maintaining compliance with conflict-of-interest policies. The researchers highlights collaboration across laboratories for experimental design, execution, and analysis.
Data and Supplementary Results
Detailed absorption spectra, cell imaging data, flow cytometry results, and computational simulations of molecular plasmons are provided as supporting evidence. All primary datasets have been made publicly available through Zenodo, and additional resources—including videos illustrating vibrational modes—are included to reinforce the mechanistic findings.
Molecular jackhammers offer a potent, rapid, and resistance-proof alternative to conventional cancer therapies by exploiting vibronic-driven mechanical disruption of cell membranes. These findings propose a paradigm shift in targeted cancer cell eradication, with compelling results in both in vitro and animal models.
Access the research paper here.
Image above: Ayala-Orozco, C., Galvez-Aranda, D., Corona, A. et al. Molecular jackhammers eradicate cancer cells by vibronic-driven action. Nat. Chem. 16, 456–465 (2024). https://doi.org/10.1038/s41557-023-01383-y
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