Molecular jackhammers eradicate cancer cells by vibronic-driven action

Area of Science:

• Biophysics
• Nanotechnology
• Oncology

Background:

• Photodynamic therapy (PDT) and photothermal therapy (PTT) are light-activated cancer treatments.
• These therapies rely on reactive oxygen species or thermal effects, respectively.
• Cancer cells can develop resistance to these mechanisms.

Purpose of the Study:

• To introduce a novel light-activated cancer cell killing mechanism.
• To investigate the efficacy of vibronic-driven action (VDA) for cancer therapy.
• To explore VDA as an alternative to PDT and PTT.

Main Methods:

• Utilized aminocyanine molecules that actuate vibronic modes upon near-infrared light exposure.
• Applied low concentrations of aminocyanines (500 nM) and low light doses (12 J cm⁻², 80 mW cm⁻² for 2.5 min).
• Assessed cell death mechanism, distinguishing it from ROS-dependent or thermal effects.

Main Results:

• VDA rapidly killed human melanoma cells in vitro via necrosis through mechanical disruption of the cell membrane.
• VDA's mechanical effect was not inhibited by reactive oxygen species scavengers.
• Achieved 50% tumor-free efficacy in mouse melanoma models.
• Demonstrated subpicosecond concerted whole-molecule vibrations of VDA-induced molecular jackhammers.

Conclusions:

• Vibronic-driven action (VDA) represents a distinct, mechanical mode of cancer cell death.
• Molecular jackhammers, inducing VDA, offer a promising alternative cancer therapy modality.
• The mechanical nature of VDA may circumvent common resistance mechanisms.