People: W. Krassowska Neu, K. Smith
Collaborators: J. Neu (UC Berkeley), S. Dev (Gene Delivery & Expression Sciences), Genetronics, Inc.
Additional information: Genetronics, Inc. Web Page
Summary:
The goals of this collaborative project are:
(1) Development of a model describing the creation and evolution of macropores,
i.e., electrically induced pores in the membrane whose radii are larger
than the radius of a DNA chain and that stay open without rupturing the
membrane for the time required for the entire chain to enter the cell.
(2) Development and implementation of a Brownian dynamics model of permeation of
DNA through such macropores. This model will be used to explore the nature
of interactions between DNA and the pore during the permeation process.
Used alongside our previously developed permeation model for small molecules,
the model of DNA permeation will help explain differences
between uptake of small drugs used in electrochemotherapy vs. long DNA
molecules used in gene therapy.
Key Publications:
W. Krassowska, J. C. Neu, and K. C. Smith,
Evolution of large electropores in presence of applied voltage,
Phys. Rev. E, submitted.
J. C. Neu and W. Krassowska, Modeling post-shock evolution of large electropores, Phys. Rev. E, submitted.
W. Krassowska and J. C. Neu, Post-shock evolution of pores, Ann. Biomed. Eng., 29: S101, 2001.
Support: NSF Grant BES-0108408 (GOALI), Genetronics, Inc., and Gene Delivery & Expression Sciences
People: W. Krassowska Neu
Collaborators: S. Dev (Gene Delivery & Expression Sciences), Genetronics, Inc.
Summary:
Success of the electroporation-based treatment is sensitive to the
proper choice of the pulsing parameters.
One must achieve a rather delicate balance between the treatment having
no effect if the field is too weak and and the cell death if the field
is too strong or applied for too long time interval.
The goal of this study was to collect a comprehensive set of data that
related lethal effects of electric fields to the duration of the pulse.
Electric pulses of different strengths and durations were applied to
a suspension of cancer cells.
Pulse durations (d) varied from 50 us to 16 ms and for each duration the
electric field that killed half of the cells (E_50) was determined.
When plotted on logarithmic axes, E_50 vs. d was a straight line,
leading to a hyperbolic relationship:
E_50 = const / d. This relationship suggests that
the total charge delivered by the pulse is
the decisive factor in killing cancer cells.
Since the strength of the electric field to which the treated tissue is exposed is one of the important parameters of the pulsing protocols, the second study used the multipole expansion to derive an analytical solution for the potential and field of a six-needle array electrode. These type of electrodes are used in pre-clinical experiments and clinical treatments of localized cancers and in gene delivery. The analytical solution matches closely the numerical solution obtained with the commercial finite element program PDEase. Thus, it is possible to estimate the fields of the electroporation electrodes without necessarily resorting to the numerical solution.
Key Publications:
W. Krassowska, G. S. Nanda, M. B. Austin, S. B. Dev, and D. P. Rabussay,
Viability of cancer cells exposed to pulsed electric fields: The role of
pulse charge,
Ann. Biomed. Eng., submitted.
S. B. Dev, D. Dhar, and W. Krassowska, Electric field of a six-needle array electrode used in drug and gene delivery in vivo: Analytical versus numerical solution, IEEE Trans. Biomed. Eng., submitted.
Support: NSF Grants BES-9974185 and BES-0108408 (GOALI), Genetronics, Inc., and Gene Delivery & Expression Sciences