期刊
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
卷 170, 期 -, 页码 140-151出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2017.04.009
关键词
Photodynamic therapy; Phthalocyanine; Spheroid; Apoptosis; Murine colon carcinoma
资金
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 066]
- Universidad de Buenos Aires [UBACYT 20020130100024]
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT-2013-0144]
Photodynamic therapy is emerging as a hopeful method for the treatment of oncological diseases. In the search of novel therapeutic strategies for colorectal cancer, in this work we reported the photocytotoxic activity of a lipophilic zinc(II) phthalocyanine on a murine colon adenocarcinoma cell line (CT26 cells). The 2,9(10),16(17),23(24) tetrakis[(2-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(Il), named Pc9, was encapsulated into Tetronic 1107 polymeric poloxamine micelles (T1107) and assayed in 2D and 3D cell cultures. We showed that the formulation Pc9-T1107 was efficient to reduce cell viability after photodynamic treatment both in 2D cultures (IC50 10 +/- 2 nM) as well as in CT26 spheroids (IC50 370 11 nM). Cellular uptake of Pc9-T1107 was a time- and concentration-dependent process, being the phthalocyanine formulation mainly incorporated into lysosomal vesicles and endoplasmic reticulum cisterns, but not in mitochondria. Pc9-T1107 also induced the formation of reactive oxygen species immediately after cell irradiation. We also found that the phototoxic action of Pc9-T1107 was partially reversed in the presence of antioxidants, such as TROLOX and N-acetyl-cysteine. In addition, we showed that Pc9-T1107 treatment triggered an apoptotic cell death, as suggested by the detection of pyknotic nuclei, the reduction in the expression levels of procaspase-3 and the increase in caspase-3 enzymatic activity.
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