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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Photodynamic therapy of human lung cancer xenografts in mice
Chukwumere Nwogu1, Paula Pera2, Wiam Bshara3
1Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York; Department of Surgery, State University of New York at Buffalo, University at Buffalo, Buffalo, New York.
Background:
There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice.
Materials And Methods:
Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis.
Results:
The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups.
Conclusions:
The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study.
Insights
A novel photosensitizer, PS1, demonstrated superior efficacy over porfimer sodium (PFII) in a preclinical study for non-small cell lung cancer (NSCLC) xenografts. PS1 treatment resulted in significantly longer tumor regrowth times and increased tumor necrosis and apoptosis.
Area of Science:
- Oncology
- Photodynamic Therapy
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) necessitates novel therapeutic strategies.
- Photodynamic therapy (PDT) is established for NSCLC palliation and is being investigated for early-stage disease.
- A new photosensitizer, PS1, was developed to potentially improve upon standard agents like porfimer sodium (PFII).
Purpose of the Study:
- To evaluate the efficacy of a novel photosensitizer, PS1, compared to porfimer sodium (PFII) in treating human lung cancer xenografts.
- To assess the impact of PS1 and PFII on tumor growth, necrosis, and apoptosis in a preclinical NSCLC model.
Main Methods:
- Human NSCLC xenografts were established in immunodeficient mice.
- Mice received either PS1 or PFII followed by laser treatment, or laser only, or no treatment (control).
- Tumor growth was monitored, and endpoints like time-to-1000 mm³ were analyzed using Kaplan-Meier and log-rank tests. Histological analysis (H&E, caspase 3) assessed necrosis and apoptosis.
Main Results:
- The median time to reach 1000 mm³ tumor volume was significantly longer in the PS1 group (52 days) compared to PFII (26 days), light only (12 days), and control (12 days) groups (P < 0.05).
- Tumor necrosis was markedly higher in the PS1 group (80%) and PFII group (67%) compared to controls.
- Caspase 3 positivity, indicating apoptosis, was also significantly higher in the PS1 group (39%) and PFII group (17%) versus controls.
Conclusions:
- The novel photosensitizer PS1 demonstrated superior antitumor activity compared to porfimer sodium (PFII) in this preclinical NSCLC xenograft model.
- PS1 treatment led to a significant delay in tumor regrowth and enhanced tumor cell death (necrosis and apoptosis).
- These findings support PS1 as a promising candidate for further investigation in NSCLC treatment.

