Electroporation based
technologies and treatments
Damijan Miklavcic, University of
Ljubljana
Abstract:
When a cell is exposed to
an electric field of sufficient amplitude its membrane becomes permeable for
molecules that otherwise are deprived of transmembrane transport mechanisms. If
electric pulse parameters are selected in a way to increase membrane
permeability only transiently, the membrane reseals and the cell survives (1).
Some chemotherapeutic drugs which have intracellular target but lack efficient
transport across the membrane (e.g. bleomycin, cisplatin) can greatly benefit
from membrane permeabilization (electroporation). Bleomycin cytotoxicity has
been demonstrated to be increased 1.000-10.000 times, whereas for cisplatin this
potentiation in vitro was 10-100 times. This potentiation of drug cytotoxicity
was effectively translated from in vitro to in vivo preclinical trials and
finally introduced into clinical practice as electrochemotherapy.
As electroporation of
membrane can be achieved in all types of cells (mammalian, bacteria and yeast)
several applications are being considered from microbial inactivation in water
treatment, fruit and vegetable juice pasteurization, enhanced extraction of
intracellular components in food processing and biotechnology, lipids extraction
from algae, to tissue ablation and gene transfer for DNA vaccination and gene
therapy (2). Recently a networking effort has been started within the COST
Action TD1104 with the aim to improve collaboration among researchers around the
world in developing and using electroporation based technologies and treatments
(3).
In 2006, a clinical device
for electrochemotherapywas put on the market and standard operating procedures
have been published for treatment of cutaneous and subcutaneous tumors. The
metastases of different origin have respondedlocally to electrochemotherapy
withoverall complete response rate of 59.4% and objective response rate of
84.1%. Since 2006, electrochemotherapy has been introduced into more than 100
clinical centers in 17 countries around Europe and is paving its way into
standard clinical use. Every year more patients are being treated by means of
electrochemotherapy with comparable results as in initial clinical trials. The
procedure is efficient, safe, well tolerated by patients and can be performed on
an outpatient basis (4).
As electroporation of
membranes of cells is achievable also in tissue and its efficiency depends
predominantly on local electric field,it is possible to treat with
electrochemotherapyalso internal tumors. Local electric field can be established
by inserting electrodes into the tissue. The “shaping” of the field by using
multiple electrodes in combination with treatment planning procedures and image
guided insertion of electrodes allows treating of solid tumors irrespective of
their location (5). Recent clinical trials in treating colorectal liver
metastasis, metastasis in bone, and soft tissue sarcoma by means of needle
electrodes proved feasibility of electrochemotherapy for deep seated tumors
making this new treatment modality a promising new tool in armamentarium of
oncologists (6).
1.
Kotnik T, Kramar
P, Pucihar G, Miklavcic D, Tarek M. Cell membrane electroporation – Part 1: The
phenomenon. IEEE Electr. Insul. M. 28(5): 14-23,
2012.
2. Haberl S, Miklavcic D,
Serša G, Frey W, Rubinsky B. Cell membrane electroporation – Part 2: The
applications. IEEE Electr. Insul. M. 29(1): 29-37,
2013.
3.
Miklavcic D. Network for development of electroporation-based technologies and
treatments. J. Membrane Biol. 245: 591-598,
2012.
4.
Mali B, Jarm T, Snoj M, Serša G, Miklavcic D. Antitumor effectiveness of
electrochemo-therapy: A systematic review and meta-analysis. Eur. J. Surg.
Oncol. 39: 4-16, 2013.
5.
Županic A, Kos B, Miklavcic D. Treatment planning
of electroporation-based medical interventions:
electrochemotherapy, gene electrotransfer and irreversible electroporation.
Phys. Med. Biol. 57: 5425-5440,
2012.
6.
Miklavcic D, Serša G, Brecelj E, Gehl J, Soden D,
Bianchi G, Ruggieri P, Rossi CR, Campana LG, Jarm T.
Electrochemotherapy: technological advancements for efficient
electroporation-based treatment of internal tumors.
Med. Biol. Eng. Comput. 50: 1213-1225,
2012.