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Updated: May 27, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Molecular determinants of photodynamic therapy for lung cancers
Jitsuo Usuda1, Shuji Ichinose, Taichirou Ishizumi
1Department of Thoracic Surgery, Tokyo Medical Universiry, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. jusuda@tokyo-med.ac.jp
Background And Objectives:
PDT induces apoptosis, inflammatory reactions, immune reactions, and damage to the microvasculature around the tumors. The mechanisms responsible for the anticancer effects of Photofrin-PDT and NPe6-PDT differ somewhat. To select a photosensitizer for lung cancer treatment and to improve the efficacy of PDT, the mechanisms of action for PDT using Photofrin or NPe6 must be elucidated and the phenomena validated by analyzing molecular determinants from clinical samples.
Study Design/Materials And Methods:
We examined the role of immunological reactions in the anti-tumor effects of PDT using cytokine-overexpressing cells and investigated whether the anti-apoptotic protein Bcl-2 may be a molecular target. Moreover, we investigated the association between ATP-binding cassette transporter proteins such as breast cancer-resistant protein (BCRP), which can pump out some types of photosensitizer, and the efficacy of PDT using clinical samples from 81 early lung cancer lesions treated with PDT between 1998 and 2006 at the Tokyo Medical University Hospital.
Results:
Photofrin-PDT damaged Bcl-2 and rapidly induced apoptosis, but NPe6-PDT did not damage Bc-2 nor did it induce morphologically typical apoptosis. However, NPe6-PDT exerted a strong anti-tumor effect, regardless of the overexpression of Bcl-2. By analyzing the BCRP-overexpressing cells, Photofrin, but not NPe6, was found to be a substrate of BCRP. All 81 lung cancer lesions were BCRP-positive; as Photofrin was found to be a substrate of BCRP, the expression of BCRP significantly affected the efficacy of Photofrin-PDT. However, NPe6-PDT exerted a strong antitumor effect regardless of BCRP expression, and the complete response rate after NPe6-PDT was much higher than that after Photofrin-PDT.
Conclusions:
Our translational research suggests that NPe6-PDT may be superior to Photofrin-PDT for the treatment of lung caner, and individualized approaches to PDT based on the expression status of Bcl-2 and/or BCRP may improve the efficacy of PDT in patients with lung cancers.
Insights
NPe6-PDT shows superior anti-tumor effects in lung cancer compared to Photofrin-PDT, irrespective of Bcl-2 or BCRP expression. Individualized PDT approaches may enhance treatment efficacy.
Area of Science:
- Oncology
- Photodynamic Therapy
- Molecular Biology
Background:
- Photodynamic therapy (PDT) utilizes photosensitizers to induce tumor cell death via apoptosis, inflammation, and microvasculature damage.
- The mechanisms of action for Photofrin-PDT and NPe6-PDT, two photosensitizers, exhibit distinct differences.
- Elucidating these mechanisms and validating molecular determinants is crucial for optimizing lung cancer PDT.
Purpose of the Study:
- To compare the anti-tumor efficacy of Photofrin-PDT and NPe6-PDT in lung cancer.
- To investigate the roles of immunological reactions and the anti-apoptotic protein Bcl-2 in PDT efficacy.
- To assess the association between ATP-binding cassette transporter proteins, specifically breast cancer-resistant protein (BCRP), and PDT outcomes.
Main Methods:
- Examined immunological reactions and Bcl-2's role in PDT using cytokine-overexpressing cells.
- Investigated the relationship between BCRP expression and PDT efficacy in 81 clinical lung cancer samples.
- Analyzed photosensitizer substrate interactions with BCRP in BCRP-overexpressing cells.
Main Results:
- Photofrin-PDT induced apoptosis and damaged Bcl-2, while NPe6-PDT did not significantly affect Bcl-2 or induce typical apoptosis but showed strong anti-tumor effects.
- Photofrin is a substrate of BCRP, and its efficacy was significantly influenced by BCRP expression in lung cancer lesions.
- NPe6-PDT demonstrated potent anti-tumor activity independent of Bcl-2 and BCRP expression, with a higher complete response rate than Photofrin-PDT.
Conclusions:
- NPe6-PDT may offer superior therapeutic benefits over Photofrin-PDT for lung cancer treatment.
- Individualizing PDT strategies based on Bcl-2 and BCRP expression levels could potentially enhance treatment outcomes in lung cancer patients.
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