Wireless molecular-electrical communications for tumor-cell-induced apoptosis

Quantum biological electron transfer (QBET) is an important biological activity that is influenced by quantum mechanical factors such as electron tunneling (ET). This mechanism, which includes cellular respiration and homeostasis, has diagnostic and therapeutic applications.

Due to a lack of technical innovation suited for spatial/temporal interaction in native biological interaction, on-demand targeted electrical-molecular communication within cells has yet to be accomplished.

In a recent study published in Nature Nanotechnology, researchers utilize electricity generated by wireless-induced redox interactions at bio-nanoantennae to cause apoptosis in cancerous cells.

Study: Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death. Image Credit: Edge Creative / Shutterstock.com

About the study

Wireless nano-electrochemical tools have been created to regulate electron transport in cancer cells, ultimately leading to cell death. In the current study, bio-nanoantennae, which are bipolar nanoelectrodes functionalized with redox-active Cytochrome c (Cyt c) and zinc porphyrin, a redox regulator, were developed.

These bio-nanoantennae can receive an external electric field (EF) input from a distance and transform it into bio-signaling events. By combining bio-nanoantennae with applied alternating current (AC) EFs, the electrodes might manipulate electron transport and transform it into molecular motion by addressing a particular metabolic pathway.

For the experiments, 100 nm PEGylated spherical gold nanoparticles (GNP100) were utilized as bipolar nanoelectrodes to electrically connect with cells at the molecular level. Transmission electron microscopy (TEM), dynamic light scattering (DLS), Zeta potential, and ultraviolet-visible light characterization revealed that GNP100 was successfully bifunctionalized with r.Cyt c and Z.

The redox molecules associated with each nanoparticle were measured. The redox behavior of r.Cyt c and Z on a bifunctionalized system were studied using cyclic voltammetry.

To investigate the potential of biological nanoantennae on alternating current-electric field-regulated redox Cyt c switching, the relationship and uptake of biological nanoantennae on different glioblastoma (GBM) cells obtained from two patients was determined. Astrocytes isolated from the human cortex were used as a non-tumorigenic cell control.

Voltage and frequency were adjusted by analyzing the changes in metabolic activities of the cancer cells as the preliminary readout of Cyt c redox switching to test the electric input that may be detected by intracellular bio-nanoantennae for generating wireless electrochemistry. To investigate the mechanism of cell death, flow cytometry and confocal microscopy (CFM) were used.

Transcriptome analysis on GBM cells and healthy cortical astrocytes was performed to better understand the molecular-electrical communication mediated at bio-nanoantennae through cordless electrochemistry.

Study findings

A distant electrical input was found to modulate electron transport across redox molecules, thereby resulting in quantum-beam electron transfer (QBET) selectively inducing death in patient-derived cancer cells. Transcriptomics data revealed that the electric field-generated bio-nanoantenna targets cancer cells specifically, demonstrating electrically induced modulation of molecular signaling.

AC-EF triggered molecular actuation through bio-nanoantennae in the therapy of an illness, which indicates that it is a quantum-functional-type medical tool. This might facilitate the development of quantum nanopharmaceuticals and cancer therapies, as well as provide a cutting-edge method of controlling cell metabolism.

The heterogeneous rate coefficient for electron transfer (k0) of Cyt c was 10 x 10^-3 cm/s, whereas it was 3.8 x 10^-3 cm/s for [email protected] c@Z 165. This observation reflects a modest reduction in Cyt c electron transfer rate in a bifunctionalized system.

After eight hours of incubation, a three-dimensional (3D) evaluation of the CFM images indicated that the biologic nanoantennae were internalized by all cell types. PrestoBlue testing demonstrated that the biologic nanoantennae were biocompatible until used at a concentration of 100 g/mL. AC-EF-sensitive bio-nanoantennae caused apoptosis in GBM cells, with the greatest effect on metabolic activity reported at 3 MHz and applied potentials of 1.0 and 0.7 volts/cm, respectively.

The reduction in metabolic activities of cells treated with [email protected] c@Z was considerably greater than that reported after a 24-hour application of United States Food and Drug Administration (FDA)-authorized tumour-treating fields (TTFs) in vitro. The change in the metabolic activities of cells treated with [email protected] c@Z as well as AC EFs of 3 MHz at 0.7 volts/cm for 12 hours, was associated with enhanced cell death.

Treatment did not affect the astrocytic transcriptome landscape; however, it modified signaling pathways unique to GBM. The mathematical modeling findings were well suited to the predicted exponential dependences for ET across a barrier, thus confirming the idea that the resonant biological effects are observed with the electrical input results in a QBET. The plasmon resonance scattering (PRS) probing plasmon resonance energy transfer (PRET) offered key experimental evidence for quantum tunneling.

Conclusions

The use of QBET, with the appropriate frequency, voltage, and linker length, allows for electrical-molecular communication. Moreover, this wireless electrochemistry-inspired device precisely targets cancer cells, which provides the foundation for future quantum-based medical diagnostics and therapies.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.