Abstract

This study examined the potential of iontophoresis in topical photodynamic therapy (PDT) of human invasive squamous cells carcinomas (SCC). SCC was induced in nude BALB/c mice by subcutaneous injection of A431 cells. Tumor penetration and distribution of the photosensitizer tetrasulfonated zinc phthalocyanine (ZnPcS4) was investigated after 10 and 30 min of in vivo iontophoresis of a gel containing ZnPcS4. PDT was performed immediately after iontophoresis using laser at 660 nm with a dose of irradiation of 100 J/cm2 and irradiance of 48 mW/cm2 while tumor growth was measured for 30 days. Iontophoresis increased ZnPcS4 penetration into tumors by 6-fold after 30 min when compared with passive delivery. Confocal microscopy analysis showed that ZnPcS4 was homogeneous distributed within deep regions of the tumor after iontophoresis. Irradiation of the tumors immediately after iontophoresis showed reduction in tumor size by more than 2-fold when compared to non-treated tumors. Iontophoretic-PDT treated tumors presented large areas of necrosis. The study concluded that iontophoretic delivery of photosensitizers could be a valuable strategy for topical PDT of invasive SCC.

Highlights

  • Squamous cell carcinoma (SCC) is a cancer of epithelial origin that begins in the squamous cells

  • We have previously demonstrated that in the absence of NaCl, cathodal iontophoresis increased about 5-fold the amount of ZnPcS4 that penetrated into the viable epidermis in comparison to the same formulation containing NaCl [5]

  • Because the amounts of drug recovered after the experiments were reliable and reproducible, we considered that this number of animals were adequate for the purpose of this experimental protocol, which was to establish an application time that makes it possible to compare ZnPcS4 penetration in the SCC after passive and iontophoretic experiments

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Summary

Introduction

Squamous cell carcinoma (SCC) is a cancer of epithelial origin that begins in the squamous cells. The major head and neck cancers and 20% of skin cancers are SCC [1,2,3]. Conventional SCC treatments involve the combination of surgery, radiation and chemotherapy. Besides these treatments mentioned above, photodynamic therapy (PDT) has provided satisfactory results in the treatment of skin cancers, its use in the treatment of nodular and invasive SCC has been avoided [4]. PDT involves the intravenous administration of a photosensitizer with affinity for cancer cells and the subsequent exposure of these cells to light at specific wavelengths; when the photosensitizer absorbs photons, a photochemical reaction is started, resulting in the production of PLOS ONE | DOI:10.1371/journal.pone.0145922. PDT involves the intravenous administration of a photosensitizer with affinity for cancer cells and the subsequent exposure of these cells to light at specific wavelengths; when the photosensitizer absorbs photons, a photochemical reaction is started, resulting in the production of PLOS ONE | DOI:10.1371/journal.pone.0145922 January 11, 2016

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