IMPROVEMENT OF CELL-LIPOSOME INTERACTION FOR PHOTODYNAMIC THERAPY

GONZÁLEZ GRAGLIA MA; SUAREZ, AI; BAUMGARTNER MT; MIRETTI, M; PRUCCA, CG

Córdoba

Congreso; LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2024

Photodynamic therapy (PDT) is a therapeutic alternative for treating several pathologies, from microbial infections tocancer. PDT involves applying a photosensitizer (PS) that interacts with light in an appropriate wavelength, absorbingits energy and going from the basal to the excited singlet state. This excited state can experience intersystem crossingto the excited triplet state (3PS*). 3PS* can generate reactive oxygen species that induce injury and trigger cell death.Phthalocyanines (Pcs) are among the most studied PSs, and although they present interesting photophysical andphotochemical properties, the main inconvenience is their hydrophobic nature, which limits their intravenousapplication. Using a transporter for the hydrophobic PSs becomes an exciting strategy with liposomes (LPs) beingwidely studied carriers composed of phospholipid bilayers. Positively charged carriers or cationic drugs increasesbinding/interaction to surfaces that exhibit anionic charges, whether bacteria or eukaryotic cells, and therefore increasesits delivery and therapeutic efficiency. The current research endeavors to investigate the benefits of enclosing ahydrophobic photosensitizer in cationic liposomes for application in a PDT protocol for glioblastoma cells, to optimizethe protocol. To accomplish this purpose, liposomes composed of DOTAP (dioleoyl-3-trimethylammonium propane),DPPC (dipalmitoylphosphatidylcholine), and cholesterol were prepared, testing the effect of two different DOTAPconcentrations on the PDT efficiency. For each formulation, 20 μM ZnPc was the final concentration inside liposomes.We measured several properties, including light absorption, size, and zeta potential for each formulation on the day ofpreparation and over time. In vitro assays were performed in multiwell plates with a final concentration of ZnPc to 0.05μM for each of the four liposomal formulations tested in T98G glioma cell lines. Dark toxicity was evaluated beforethe PDT protocol, finding appropriate cell viability in the absence of irradiation in all the concentrations assessed. Cellirradiation was performed at different incubation times for all formulations of interest. Cellular viability monitored 24hours after irradiation, showed differences between neutral and cationic liposomes, the latter being the ones that showedenhanced cellular death with shorter incubation periods. The findings underscore the exciting potential of theseinnovative formulations for more efficiently delivering photodynamic therapy to treat glioblastoma.