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Published on: December 15, 2010
Nanosecond pulses targeting intracellular ablation increase destruction of tumor cells with irregular morphology
Chenguo Yao1, Junyi Ning1, Hongmei Liu1
1Chongqing University, College of Electrical Engineering, Chongqing 400030, China.
Abstract:
The decrease in killing sensitivity of the cell membrane to microsecond pulse electric fields (μs-PEFs) is ascribed mainly to the aberrant morphology of cancer cells, with clear statistical correlations observed between cell size and shape defects and the worsening of the electrical response to the PEF. In this paper, nanosecond pulsed electric fields (ns-PEFs) inducing the nucleus effect and μs-PEFs targeting the cell membrane were combined to enhance destruction of irregular cells. The fluorescence dissipation levels of the nuclear membrane and cell membrane exposed to the μs, ns, and ns + μs pulse protocols were measured and compared, and a dynamic electroporation model of irregular cells was established by the finite element software COMSOL. The results suggest that the cell membrane disruption induced by μs-PEFs is worse for extremely irregular cells and depends strongly on cellular morphology. However, the nuclear membrane disruption induced by ns-PEFs does not scale with irregularity, suggesting the use of a combination of ns-PEFs with μs-PEFs to target the nuclear and cell membranes. We demonstrate that ns + μs pulses can significantly enhance the fluorescence dissipation of the cell and nuclear membranes. Overall, our findings indicate that ns + μs pulses may be useful in the effective killing of irregular cells.
Insights
Combining nanosecond and microsecond pulsed electric fields (nsPEFs and μsPEFs) effectively destroys irregular cancer cells. This dual-pulse approach targets both the cell and nuclear membranes, enhancing cell killing sensitivity.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Cancer cell morphology, specifically size and shape defects, correlates with reduced cell membrane sensitivity to microsecond pulsed electric fields (μs-PEFs).
- Aberrant cell morphology poses a challenge for effective cancer cell destruction using conventional electroporation techniques.
Purpose of the Study:
- To investigate the combined effects of nanosecond pulsed electric fields (ns-PEFs) and μs-PEFs on irregular cancer cells.
- To enhance the destruction of cancer cells with aberrant morphologies by targeting both the cell and nuclear membranes.
Main Methods:
- Experimental measurement of fluorescence dissipation in cell and nuclear membranes under μs-PEFs, ns-PEFs, and combined ns + μs pulse protocols.
- Development of a dynamic electroporation model for irregular cells using COMSOL finite element software.
Main Results:
- μs-PEFs-induced cell membrane disruption is significantly impaired in highly irregular cells, depending heavily on cell morphology.
- ns-PEFs-induced nuclear membrane disruption is independent of cell irregularity.
- Combined ns + μs pulses significantly enhance fluorescence dissipation in both cell and nuclear membranes.
Conclusions:
- The combination of ns-PEFs and μs-PEFs offers a promising strategy for overcoming the reduced sensitivity of irregular cancer cells to electroporation.
- This dual-pulse approach effectively targets both the cell membrane and the nucleus, leading to enhanced cancer cell destruction.
- ns-PEFs combined with μs-PEFs may represent a novel therapeutic approach for treating cancers with heterogeneous or irregular cell populations.
