Antitumor activity of photodynamic therapy with tetracationic derivative of synthetic bacteriochlorin in spheroid culture of liver and colon cancer cells

合成菌绿素四阳离子衍生物光动力疗法在肝癌细胞和结肠癌细胞球体培养中的抗肿瘤活性

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作者:Saida Sh Karshieva, Elizaveta G Glinskaya, Alexandra A Dalina, Ekaterina V Akhlyustina, Elena A Makarova, Yusef D Khesuani, Nelly S Chmelyuk, Maxim A Abakumov, Dmitriy A Khochenkov, Vladimir A Mironov, Gennady A Meerovich, Evgeniya A Kogan, Elizaveta V Koudan

Abstract

Efficient screening of photosensitizers (PS) as well as studying their photodynamic activity, especially PS excited in the near-infrared region, require informative in vitro models to adequately reflect the architecture, thickness, and intercellular interactions in tumors. In our study, we used spheroids formed from human colon cancer HCT-116 cells and liver cancer Huh7 cells to assess the phototoxicity of a new PS based on tetracationic derivative of synthetic bacteriochlorin (BC4). We optimized conditions for the irradiation regime based on the kinetics of BC4 accumulation in spheroids and kinetics of spheroid growth. Although PS accumulated more efficiently in HCT-116 cells, characterized by more aggressive growth and high proliferative potential, they were less susceptible to the photodynamic therapy (PDT) compared to the slower growing Huh7 cells. We also showed that 3D models of spheroids were less sensitive to BC4 than conventional 2D cultures with relatively identical kinetics of drug accumulation. Our findings suggest that BC4 is a perspective agent for photodynamic therapy against cancer cells.

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