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Evaluation of a bacteriochlorin-based photosensitizer’s anti-tumor effect in vitro and in vivo

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Bacteriochlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. In the current study, the photodynamic activity of a novel bacteriochlorin derivative, cis-2, 3, 12, 13-tetracarboxymethyl-5, 10, 15, 20-tetraphenyl bacteriochlorin (TCTB), was evaluated both in vitro and in vivo.

Methods

Physicochemical characteristics of the novel photosensitizer were measured. The efficiency of TCTB-PDT in vitro was analyzed by MTT assay, clonogenic assay and in situ trypan blue exclusion test. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The accumulation of TCTB in human malignant tumor cells was measured by fluorescence spectrometer, and the pathway of cell death was analyzed by flow cytometry. S180 tumor model was used to evaluate the anti-tumor effects of TCTB-PDT. And histopathological study was also used to confirm the anti-tumor effect.

Results

TCTB shows a singlet oxygen quantum yield of 0.56 and displays a characteristic long wavelength absorption peak at 732 nm. The accumulation of TCTB increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. In vitro PDT using TCTB and Nd:YAG laser showed drug concentration-, laser dose-dependent cytotoxicity to human esophageal cancer Eca-109 cells. In mice bearing osteosarcoma S180 tumors, the combined use of 10 mg/kg TCTB and 120 J/cm2 showed superior anti-tumor activity. Histology examination of tumor tissues revealed that PDT using TCTB and the Nd:YAG laser induced tumor cells shrunken and necrotic.

Conclusion

In in vitro and in vivo studies, we found that TCTB has excellent anti-tumor effect. It suggests that TCTB is a potential photosensitizer of PDT for cancer.

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Acknowledgments

This work was supported by Chinese National Natural Science Foundation (21372042, 81101298, 81301878), Foundation of Shanghai government (13431900700, 14431906200, 13430722300, 14140903500, 13ZR1441000, 13ZR1440900, 14ZR1439800, 14ZR1439900, 201370) and Foundation of Yiwu Science and Technology Bureau (2011-G1-15, 2013-G3-03, 2012-G3-02).

Conflict of interest

We declare that we have no conflict of interest in relation to this article.

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Authors and Affiliations

  1. Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, People’s Republic of China

    Li-Jun Zhang, Chun-Ye Zhang, Li Wang & Zhi-Long Chen

  2. Center for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland

    Donal O’Shea

  3. Shanghai Xianhui Pharmaceutical Co. Ltd, Shanghai, 200433, People’s Republic of China

    Yi-Jia Yan

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  1. Li-Jun Zhang
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Correspondence to Zhi-Long Chen.

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Zhang, LJ., O’Shea, D., Zhang, CY. et al. Evaluation of a bacteriochlorin-based photosensitizer’s anti-tumor effect in vitro and in vivo. J Cancer Res Clin Oncol 141, 1921–1930 (2015). https://doi.org/10.1007/s00432-015-1960-z

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  • DOI: https://doi.org/10.1007/s00432-015-1960-z

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