Chlorin e6 – polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts

William Wl Chin,Malini Olivo,Paul Ws Heng

doi:10.1186/1471-2210-7-15

Abstract

BackgroundPhotodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung cancers. The present study evaluated the potential use of chlorin e6 – polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC xenografts.ResultsHuman NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines were used to establish tumor xenografts in the chick chorioallantoic membrane (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was applied topically (1.0 mg/kg) and fluorescence intensity was charted at various time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6-PVP has a selective localization and a good accuracy in demarcating NSCLC compared to SCLC from normal surrounding CAM after 3 h post drug administration. Irradiation at 3 h drug-light interval showed greater tumor necrosis against human NSCLC xenografts in nude mice. SCLC xenografts were observed to express resistance to photosensitization with Ce6-PVP.ConclusionThe formulation of Ce6-PVP is distinctly advantageous as a diagnostic and therapeutic agent for fluorescence diagnosis and PDT of NSCLC.

Highlights

Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death
Photosensitization with chlorin e6 – polyvinylpyrrolidone (Ce6-PVP) for 3 hours of exposure time appeared to be most effective in detecting non-small cell lung carcinoma (NSCLC) in chorioallantoic membrane (CAM) model
PDT at 3 h drug-light interval resulted in a better tumor necrosis in NSCLC xenograft model

Summary

Introduction

Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. BMC Pharmacology 2007, 7:15 http://www.biomedcentral.com/1471-2210/7/15 ess that results in the generation of highly cytotoxic species including singlet oxygen The release of these reactive molecules results in damage to both tumor cells and to the tumor microenvironment. The significance of PDT is that there is a degree of treatment selectivity that allows tumor destruction with minimal involvement of healthy tissue. This is achieved by a combination of selective accumulation of photosensitizer within the tumor and by control of the light geometry and illumination parameters [2]

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Conclusion