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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Photodynamic therapy of disseminated non-small cell lung carcinoma in a murine model
Craig E Grossman1, Stephen Pickup, Amy Durham
1Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA.
Background And Objective:
Photodynamic therapy (PDT) of thoracic malignancies involving the pleural surfaces is an active area of clinical investigation. The present report aims to characterize a model for PDT of disseminated non-small cell lung carcinoma (NSCLC) grown orthotopically in nude mice, and to evaluate the effect of PDT on tumor and normal tissues.
Study Design:
H460 human NSCLC cells were injected percutaneously into the thoracic cavity of nude mice. HPPH-PDT (1 mg/kg, 24 hours) was performed via the interstitial delivery (150 mW/cm) of 661 nm light to the thoracic cavity at fluences of 25-200 J/cm.
Results:
H460 tumors exhibited exponential growth within the thoracic cavity consisting of diffuse, gross nodular disease within 9 days after intrathoracic injection. Tumor volume, measured by magnetic resonance imaging (MRI), was highly correlated with the aggregate tumor mass extracted from the corresponding animal. Intrathoracic PDT at fluences of ≥50 J/cm produced significant decreases in tumor burden as compared to untreated controls, however, mortality increased with rising fluence. Accordingly, 50 J/cm was selected for MRI studies to measure intra-animal PDT effects. Tumor distribution favored the ventral (vs. dorsal), caudal (vs. cranial), and right (vs. left) sides of the thoracic cavity by MRI; PDT did not change this spatial pattern despite an overall effect on tumor burden. Histopathology revealed edema and fibrin deposition within the pulmonary interstitium and alveoli of the PDT-treated thoracic cavity, as well as occasional evidence of vascular disruption. Prominent neutrophil infiltration with a concomitant decline in the lymphocyte compartment was also noted in the lung parenchyma within 24 hours after PDT.
Conclusion:
HPPH-PDT of an orthotopic model of disseminated NSCLC is both feasible and effective using intracavitary light delivery. We establish this animal model, together with the treatment and monitoring approaches, as novel and valuable methods for the pre-clinical investigation of intrathoracic PDT of disseminated pleural malignancies.
Insights
Photodynamic therapy (PDT) effectively reduced non-small cell lung carcinoma (NSCLC) tumor burden in an orthotopic mouse model. This study establishes a valuable preclinical model for investigating intrathoracic PDT of pleural malignancies.
Area of Science:
- Oncology
- Photodynamic Therapy
- Preclinical Research
Background:
- Photodynamic therapy (PDT) is under investigation for thoracic malignancies.
- Disseminated non-small cell lung carcinoma (NSCLC) involving pleural surfaces presents a treatment challenge.
Purpose of the Study:
- To characterize an orthotopic mouse model of disseminated NSCLC.
- To evaluate the efficacy and effects of photodynamic therapy (PDT) on tumors and normal tissues within the thoracic cavity.
Main Methods:
- H460 human NSCLC cells were injected into the thoracic cavity of nude mice.
- HPPH-PDT was administered using interstitial light delivery at various fluences.
- Tumor volume was monitored using magnetic resonance imaging (MRI).
Main Results:
- Intrathoracic PDT significantly decreased tumor burden at fluences of ≥50 J/cm², though higher fluences increased mortality.
- MRI revealed tumor distribution patterns unaffected by PDT, despite overall tumor reduction.
- Histopathology showed edema, vascular disruption, and inflammatory cell infiltration in PDT-treated lungs.
Conclusions:
- HPPH-PDT is feasible and effective for treating disseminated NSCLC in an orthotopic model.
- This model and associated methods are valuable for preclinical studies of intrathoracic PDT for pleural malignancies.

