Effectiveness of ZnPc and of an amine derivative to inactivate Glioblastoma cells by Photodynamic Therapy: an in vitro comparative study

VELAZQUEZ, FABIOLA N.; MIRETTI, MARIANA; BAUMGARTNER, MARIA T.; CAPUTTO, BEATRIZ L.; TEMPESTI, TOMAS C.; PRUCCA, CÉSAR G.

Scientific Reports

Springer

Año: 2019 vol. 9

Glioblastoma multiforme is considered to be one of the most aggressive types of tumors of the centralnervous system, with a poor prognosis and short survival periods of ~ one year. The current protocolfor glioblastoma treatment includes the surgical excision of the primary tumor followed by radio andchemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatmentof several types of tumors. Phthalocyanines (Pcs) are good photosensitizers (PSs) for PDT becausethey induce cell death in several cellular models. ZnPc (Zn(II)phthalocyanine) is a well-known Pc,extensively tested in different cells and tumor models, but its evaluation on a glioblastoma modelhas been poorly studied. Herein, we compare the capacity of ZnPc and one of its derivatives, Zn(II)tetraminephthalocyanine (TAZnPc), to photoinactivate glioblastoma cells (T98G, MO59, LN229 andU87-MG) in culture. We measured the cellular uptake, the toxicity in the dark and the subcellularlocalization of the different Pcs, as well as the clonogenic capacity of surviving cells after PDT. Themechanism of cell death induced after PDT was determined by measuring caspase 3 activation, DNAfragmentation, phosphatidylserine externalization, mitochondrial morphological changes and loss ofmitochondrial membrane potential as well as lysosomal membrane integrity. Overall, ZnPc and TAZnPcpresent good properties to be used as PSs with photoinactivation capacity on glioblastoma cells