Abstract
The aim of our study was to determine if electroporation could improve the efficacy of photodynamic tumor therapy. A disadvantage of photodynamic therapy is a slow and in some cases insufficient accumulation of photosensitizer in tumor tissue, which could restrict the achievement of an efficient dose. Under the action of electric pulses, cells undergo membrane electroporation, which results in an increased permeability to various exogenous molecules. In this study, murine hepatoma MH22A cells were exposed to light in vitro in the presence of a photosensitizer, either chlorin e6 or aluminum phthalocyanine tetrasulfonate, following electroporation. Accumulation of the photosensitizers was registered by fluorescence microscopy. Cell viability was determined by the MTT assay. Our results demonstrate that electroporation improves an access of chlorin e6 and aluminum phthalocyanine tetrasulfonate to MH22A cells. Electroporation in combination with photosensitization significantly reduces viability of the treated cells even at low doses of photosensitizers.
Highlights
When a cell is exposed to short and strong external electric pulses, the anode-facing side becomes hyperpolarized, and the cathode-facing side becomes depolarized, and cell membrane undergoes a remodeling process characterized by the occurrence of transient permeation structures – “electropores” [1, 2]
To evaluate the influence of electroporation on the access of photosensitizers to tumor cells, the murine hepatoma MH22A cells were incubated with the photosensitizers AlPcS4 and Chlorin e6 (C e6) and exposed to electric pulses
A fluorescence microscopy revealed an insignificant amount of C e6 incorporated in plasma membrane of cells that were not exposed to electric pulses (Fig. 2, C e6)
Summary
When a cell is exposed to short and strong external electric pulses, the anode-facing side becomes hyperpolarized, and the cathode-facing side becomes depolarized, and cell membrane undergoes a remodeling process characterized by the occurrence of transient permeation structures – “electropores” [1, 2]. Membrane electroporation offers an approach for enhanced drug delivery into the cells and better antitumor effectiveness This new approach, termed electrochemotherapy (ECT), was introduced by Okino and Mir [7]. It has been shown that in vitro cytotoxicity of some chemotherapeutic drugs can be potentiated several hundred-fold by exposing cells to short intense electric pulses [8, 9]. It has been proposed in many instances that ECT can be very efficient even with highly reduced doses of chemotherapeutic drug, which in turn almost completely eliminate adverse side effects of the drug. Bleomycin at these concentrations is ineffective without application of electric pulses
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