New Efficient Nanostructural Near-IR Photosensitizer for Photodynamic Therapy of Malignancies based on Micellar Dispersion of Zinc octa-4,5-decylthio-octa-3,6-chlorophthalocyanine I. Meerovich * , K. Volkov ** , G. Meerovich *** , E. Lukyanets ** , V. Negrimovsky ** , S. Barkanova ** , L. Umnova ** , V. Loschenov *** , N. Oborotova * , G. Vorozhtsov ** and A. Baryshnikov * * N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russia, igor_meer@mail.ru ** State Research Center "NIOPIK", Moscow, Russia, rmeluk@niopik.ru *** A.M. Prokhorov General Physics Institute of RAS, Moscow, Russia, meerovich@mail.ru ABSTRACT The work is devoted to the investigation of new nanostructural photosensitizer based on phthalocyanine derivative – zinc octa-4,5-decylthio-octa-3,6-chloro- phthalocyanine with absorption maximum at 730 nm. Active substance was solubilized in micellar form based on non-ionic Pluronic-like surfactant. Nanostructural properties of dispersions were studied by means of correlation laser spectrometry. Optimization of content and proportion of components allowed us to achieve high stability of nanostructural properties of dispersion stored at room temperature. Dynamics and selectivity of photosensitizer accumulation in tumor and normal tissue were estimated in vivo from absorption spectra of sensitized tissue measured by diffuse reflectance approach. Photosensitizer selectively accumulates in tumors. For PDT, they were irradiated using 732 nm laser with power density in a range of 100-300 mW/cm 2 for 20 min. Tumor growth inhibition for Ehrlich tumor exceeded 80%. Keywords: photodynamic therapy, photosensitizer, phthalocyanine, micellar dispersion, absorption 1 INTRODUCTION Methods of photodynamic therapy (PDT) and fluorescence diagnostics of malignancies are widely investigated for experimental and clinical oncology. High photodynamic efficiency, suitable spectral range, high quantum yield of fluorescence and photostability play the important role for the choice of photosensitizer for photodynamic therapy. Photosensitizers absorbing in the spectral range of 720-850 nm provide the greatest depth of photodynamic effect due to the minimal intrinsic absorbance of non-sensitized tissue in this range. Additional factor determining a choice of suitable spectral range for PDT is an availability of accessible sources of laser radiation in this range (in particular, laser diodes). The work is devoted to the investigation of new perspective compound of alkylthio-substituted phthalocyanines series for development of photosensitizers of near-infrared range based on nanostructural dispersions. 2 MATERIALS AND METHODS In this work we have conducted the in vivo investigation of zinc octa-4,5-decylthio-octa-3,6-chlorophthalocyanine [(DecS) 8 Cl 8 PcZn] which Q y absorption maximum is located around 730 nm. The structure of the photosensitizer is shown on Fig. 1. N N N N C 10 H 21 S Cl SC 10 H 21 SC 10 H 21 Cl Cl SC 10 H 21 SC 10 H 21 Cl Cl C 10 H 21 S C 10 H 21 S Cl Cl C 10 H 21 S Cl Zn Figure 1: Chemical structure of zinc octa-4,5-decylthio-octa-3,6-chlorophthalocyanine. For intravenous administration of hydrophobic (DecS) 8 Cl 8 PcZn, we have prepared its micellar dispersion on a base of non-ionic Pluronic-like surfactant. Particle size distribution was estimated by means of laser correlation spectrometry method using LCA-3 (Russia) and NICOMP CW-380 (USA) devices. These studies have shown that micelles had uniform size distribution with mean size in a range of 210-220 nm remaining stable for long time of storage under room temperature (Fig. 2). The examination of sensitized biological tissue and photodynamic treatment were performed on F 1 hybrid mice bearing Ehrlich (ELD) tumor inoculated intramuscularly on right flank 4-5 days before administration of photosensitizer. NSTI-Nanotech 2008, www.nsti.org, ISBN 978-1-4200-8504-4 Vol. 2 38