Dr. Barbara Pucelik Profile

Dr. Barbara Pucelik

at Jagiellonian Univ. in Krakow

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Proceedings Article | 14 August 2019 Presentation

The impact of photodynamic therapy therapy with polarity-tunable bacteriochlorins on the antitumor immunity: local effects and systemic consequences (Conference Presentation)

Janusz Dabrowski, Barbara Pucelik, Luis G. Arnaut

Proceedings Volume 11070, 1107061 (2019) https://doi.org/10.1117/12.2526642

KEYWORDS: Photodynamic therapy, Tumors, Biological research, Molecular mechanisms, Spectroscopy, In vitro testing, Cell death, In vivo imaging, Inflammation, Picosecond phenomena

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The main goal of this study is to analyze photochemical and molecular mechanisms of PDT with the set of polarity-tunable bacteriochlorins. The relationship of the structure and biological activity of the tested bacteriochlorins (F2BOH, F2BMet, F2BPrc, Cl2BHep) was determined, including (i) physicochemical, spectroscopic and photophysical characterization; (ii) the analysis of in vitro activity (cytotoxicity, subcellular localization, cell death modes); and (iii) the photodynamic efficacy in vivo (vascular versus cellular targeting). A detailed analysis of PDT-induced inflammation and a full characterization of molecular mechanisms were performed. The differences in the efficacy of the chosen phototherapeutic protocols (V-PDT, E-PDT, C-PDT) with optimized PDT conditions (Ps formulation, DLI, light dose) are demonstrated. To elucidate these differences, a Luminex technology was applied to detect a number of cytokines in the tumor and in plasma of PDT-treated mice. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15) and chemokines (KC, MIP1, MIP2) released after PDT, an important role is assigned to IL-6. Moreover, expression of recombinant cytokines such as GM-CSF and TNFα significantly enhance antitumor response, whereas blocking anti-inflammatory cytokines such as IL-10 or VEGF improves the cure rates after PDT. Bacteriochlorin-mediated PDT generates specific immune response capable of inducing immunological memory that enables mice to reject a tumor rechallenge. Moreover, we have demonstrated that PDT activates innate and adaptive immunity that result in the eradication of NIR-irradiated primary tumors and the inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T-cell response.

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