Evaluation of ZnPc and one aminoderivate effectiveness for PDT on glioblastoma cells

MIRETTI, M; CAPUTTO,BL; BAUMGARTNER,MT; PRUCCA, C.G.; VELAZQUEZ,FN; TEMPESTI, T

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. LIII Reunion Anual de la Sociedad Argentina de Investigaciones en Bioquimica y Biologia Molecular.; 2017

Glioblastoma multiforme is a type of tumor of the central nervoussystem (CNS), known for being one of the worst and fast-growingbrain tumor. This type of cancer presents a poor prognosis after diagnosiswith a survival rate of approximately one year. The currentprotocol for glioblastoma treatment consists in the surgical excisionof the primary tumor followed by radio and chemotherapy. Photodynamictherapy (PDT) is a well-known therapeutic approach thatcombine two components (light and a photosensitizer (PS)) to inducecell death triggered by singlet oxygen (1O2) and/or reactive oxygenspecies (ROS) as a result of photochemical reactions. Phthalocyanines(Pcs), are excellent second generation photosensitizersfor PDT. They present a far red wavelength absorption (>670 nm),long triplet lifetime (~1 ms), and high quantum yields of singlet oxygengeneration (>0.2). In this work, we compared the capacity ofZnPc and one of its derivatives (TAZnPc) to photo inactivate glioblastomacells in vitro. We analyzed the photochemical propertiesof both PS, their incorporation, subcellular localization and we observeda relation with the mechanism of cell death induced afterillumination: ZnPc associate more to mitochondria compared tothe TAZnPc which present a markedly lysosomal localization. Wecompared the clonogenic capacity after PDT, the type of cell deathtriggered, the molecular signals associated to them and the cellularorganelles damaged after PDT. Also, both Pcs were vehiculizatedinto DPPC-cholesterol liposomes and measured the PDT capacityof both PS compared to the DMF administration. In summary, ZnPcresults more efficient to photoinactivate glioblastoma cells in vitro,perhaps due to its subcellular localization and singlet oxygen generation,however, TAZnPc absorb in a longer wavelength allowing theirradiation with greater wavelength assuring a deep action in tissueby the PS (application in vivo).