Regression of the murine LM3 tumor by repeated photodynamic therapy with meso-tetrakis-(4-N,N,N-trimethylanilinium)porphine

Abstract

Photodynamic therapy (PDT) of cancer is based on the cytotoxicity induced by a photosensitizer (PS) in the presence of oxygen and visible light, with formation of reactive oxygen species which cause cell death and tumor destruction. This work describes the response of the murine mammary adenocarcinoma, LM3, to repeated PDT using meso-tetrakis(4-N,N,N-trimethylanilinium)porphine (TMAP), a PS that has been overlooked for PDT applications. Intradermal LM3 tumors in BALB/c mice (controls) were left untreated, only treated with light, only injected with 0.9% NaCl solution or with TMAP alone (10 μg/0.1 ml). For PDT, the intratumoral PS injection was followed 1 h later by blue-red light irradiation (290 J.cm-2). In all cases, control and PDT treatments were performed on the depilated and glycerol-covered skin which covers the tumor of anesthetized animals, and repeated 4 times (every 2 days). No significant differences were found in the growth rate of all control tumors. PDT-treated tumors showed complete and long-term regression in 4 out of 5 mice, and cure in one animal. The survival of PDT-mice was significantly longer than that of controls (TMAP alone), showing a lower number of tumor-draining lymph node metastasis. The PDT protocol applied in the present work (intratumoral PS injection, repeated photosensitizing treatments, and reduction of tissue light scattering by glycerol) could be a useful strategy in studies on PDT of cancer.