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

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/cm(2) 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.

• Authors: Li-Jun Zhang, Donal O'Shea, Chun-Ye Zhang, Yi-Jia Yan, Li Wang, Zhi-Long Chen
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 11 Pg. 1921-30 (Nov 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25804838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,3,12,13-tetracarboxymethyl-5,10,15,20-tetraphenylbacteriochlorin
• Antineoplastic Agents
• Photosensitizing Agents
• Porphyrins
• bacteriochlorin

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Apoptosis
• Cell Line, Tumor
• Humans
• Mice
• Neoplasms (drug therapy, pathology)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacokinetics, therapeutic use)
• Porphyrins (pharmacokinetics, therapeutic use)