NEW APPROACHES FOR GLIOBLASTOMA TREATMENT USING PHOTODYNAMIC THERAPY

PRUCCA CG

Córdoba

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

Glioblastoma (GBM) is the most aggressive tumor originating from the malignant transformation of cells in the centralnervous system. GBM diagnosis is tragically linked to a poor prognosis, typically resulting in overall survival of only12-14 months following standard treatment (surgery, followed by radio and chemotherapy using Temozolomide).However, despite numerous global efforts, the survival rate of patients has not significantly improved in recent years.This emphasizes the necessity for new or enhanced therapeutic approaches. Photodynamic therapy (PDT) is a noveland attractive therapeutic approach that combines three harmless components: light, oxygen, and a photoactivatablecompound known as a photosensitizer (PS). Combined, these components induce cell injury and trigger cell deaththrough photochemical reactions, generating singlet oxygen (1O2) and/or reactive oxygen species (ROS). Unlike otherantitumor approaches, PDT confines its action to the irradiation site, avoiding undesirable side effects observed in classical therapeutics. In our laboratory, we studied novel PSs, liposomal formulations for PS delivery, and mechanismsand genes associated with the effectivity of PDT. Recently, we showed that using two different phthalocyaninephotosensitizers could effectively inactivate several glioblastoma cell lines, primarily inducing cell death throughapoptosis. We examined the photochemical properties of both PSs, their uptake, and subcellular localization. Weobserved a correlation between the above-mentioned parameters and the mechanism of cell death induced afterirradiation. Furthermore, we discovered that enclosing the PSs in liposomes made of dipalmitoylphosphatidylcholine(DPPC) and cholesterol significantly improved the efficiency of the PDT. We are currently analyzing new liposomeformulations to enhance the delivery of PS into cells. Several therapies have been improved if they are synchronizedwith the circadian rhythms. Recent findings from our team indicate that the effectiveness of PDT in eliminating GBMcells is influenced by the cell’s inner clock, underscoring the potential of this approach to enhance therapeutic outcomes.