Enhancement of photodynamic tumor therapy effectiveness by electroporation in vitro.

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.

[The role of electroporation in increasing the effectiveness of anticancer drugs]. / Elektrochemoterapijos vaidmuo didinant vaistu nuo vezio veiksminguma

By applying electric pulses to tumor the membrane of tumor cells undergoes destabilization that enables the drug molecules to enter into the cells more freely and selectivity of anticancer drugs increases. Thus, administering smaller doses of anticancer drugs it might be possible to achieve a better therapeutic effect and to reduce side effects of cytostatic therapy. Such combination of chemotherapy with electric pulses is called electrochemotherapy. The aim of this study was to evaluate the anticancer effectiveness of single and repeated courses of electrochemotherapy with three different anticancer agents (cyclophosphamide, carboplatinum and bleomycin) using experimental animals. It was established that electrochemotherapy used as a single treatment the best increases cytotoxicity of bleomycin. While applying the electrochemotherapy course for 5 days all investigated anticancer drugs showed higher cytotoxicity as compared to the effect of these cytostatics without electroporation. It is notable that in this case antitumor effect of bleomycin was the highest--99% of treated tumors showed a high response rate and no recurrence was observed for 30 days.

Autofluorescence of transplantable hepatoma A22 (MH-A22): prospects of tumor tissue optical biopsy.

AIM: Autofluorescence of experimental tumor (hepatoma A22 (MH-A22)) was employed to discriminate the optical differences between necrotic and non-necrotic tumor, hemorrhagic tumor and healthy tissue. METHODS: The experiment was performed ex vivo using the transplantable tumor from the right haunch of hybrid mice (C57Bl/CBA). Blue LED light (lambda em=405 nm) was applied for autofluorescence excitation and fibre optics based spectrofluorimeter was used for spectra detection. RESULTS: We observed that necrotic tumor tissue is characterized by the absence of endogenous porphyrins fluorescence, and registered spectra do not possess differences in the red spectral region (600-710 nm) in comparison with normalized autofluorescence spectra of muscle. Moreover, only certain segments of non-necrotic tumor bear the fluorescence of endogenous porphyrins. CONCLUSIONS: Based on the experimental results, we suggest that the absence of long-waved fluorescence differences between necrotic tumor tissue and healthy tissue, e.g. muscle can impede the demarcation between healthy and tumor tissue. The uneven distribution of endogenous porphyrins in non-necrotic tumor tissue as well as the absence of endogenous porphyrins fluorescence in the small experimental tumors complicates the localization of cancerous tissue based on the autofluorescence registration.