Photodynamic therapy of oncogene-transformed cells

Area of Science:

• Oncology
• Biomedical Engineering
• Photochemistry

Background:

• Photodynamic therapy (PDT) utilizes photosensitizers and light to induce cell death.
• Dihematoporphyrin ether (DHE) is a photosensitizer used in PDT.
• Kirsten ras oncogene-transformed cells provide a model for studying PDT efficacy.

Purpose of the Study:

• To establish and validate a novel in vitro and in vivo photodynamic therapy (PDT) model using a Kirsten ras oncogene-transformed cell line (45342).
• To evaluate the sensitivity of these transformed cells to PDT.
• To optimize DHE delivery and assess PDT effects in a murine allograft model.

Main Methods:

• In vitro colony formation assays to assess cell survival after DHE incubation and light exposure.
• Establishment of subcutaneous 45342 allografts in nu/nu mice.
• Comparison of intravenous (IV) versus intraperitoneal (IP) DHE administration.
• Analysis of DHE tissue kinetics and tumor retention.
• In vivo PDT treatment with specific light dose and power density.

Main Results:

• DHE and 630 nm light alone did not affect 45342 cell survival.
• In vitro PDT demonstrated significant cytotoxicity (90% at 950 J/m2, 99% at 1575 J/m2).
• IV DHE administration resulted in higher sensitizer levels and less variation compared to IP.
• Selective DHE retention in tumors was observed at 24 hours post-injection.
• In vivo PDT induced tumor necrosis and regression.

Conclusions:

• Transformed malignant cells exhibit sensitivity to photodynamic therapy.
• The developed 45342 cell line model is suitable for in vitro and in vivo PDT studies.
• Intravenous DHE delivery and targeted light application are effective for tumor regression.