„Role of multidrug resistance transporters in photodynamic effect induced by chlorophyll derivatives”
Project supported by the National Science Centre, Poland under the „PRELUDIUM 10” programme
Total cost: 150 000,00 PLN
Centre Contribution: 150 000,00 PLN
Duration: 30/11/2016 – 29/11/2019
Principal Investigator: mgr Milena Szafraniec
The project will focus on BCRP, one of the most important xenobiotic transporters, which are among the main elements of the defense system against toxins in mammals, being at the same time the cause of unwanted multidrug resistance. The activity of analogous transporters in bacteria and fungi brings about their resistance against antibiotics and antifungal agents. Therefore it essential to understand the action of these proteins. The outcome of the project will contribute to a better understanding of the mechanisms of action of the ABC transporters, which is relevant also to the efficacy of photodynamic therapy and other therapies.
The aim of the project is to clarify whether and how the activity of human xenobiotic transport system (XTS) affects the efficacy of photodynamic therapy (PDT). This will be realized by finding the relationships between the structure of photosensitizers (derivatives of chlorophylls, Chls), their recognition by transport proteins (BCRP, P-glycoprotein, MRP1) and the strength of photodynamic effect in cells. The substrate-transporter interactions and structure-activity relationships will be analyzed in human cells in vitro and in model system consisting of human BCRP reconstituted in liposomes. My research hypothesis, that XTS determines the efficacy of PDT using Chls-derivatives and its interactions with the photosensitizers depend on their structure, is based on the results obtained earlier in our group. Therefore, the modifications of Chls will be done with the aim to affect the interactions with XTS. The realization of the project will contribute to a better understanding of cellular defense mechanisms against stresses induced by photocytotoxic xenobiotics/metabolites. In particular, it will allow us to clarify the role of xenobiotic transporters as factors limiting the outcome of photodynamic therapy and other therapies.