Abstract 3709: Synthesis of chlorin-based fatty acid conjugate as photosensitizer for photodynamic therapy

Abstract

Abstract Photodynamic therapy (PDT) is promising an approach to cancer treatment that requires the combination of photosensitizer (PS), tissue oxygen, and light. Many PSs have been developed for the PDT; however, very few have made in clinical trials because improved drugs that are more selective and that can be used conveniently and without sustained skin photosensitivity are needed. Tumor targeting drug delivery is another attractive strategy in cancer treatment. In this study, our purpose is to improve their selectivity on tumor cell as conjugating of chlorin-based PSs with unsaturated fatty acids (UFAs) that are taken up rapidly by tumors from the arterial blood, presumably for use as biochemical precursors and energy sources. We have selected methyl pyropheophorbide-d-OH (MPPd) and pyropheophorbide-a-173-N-hexanol (PPa-N-He) that possess reactive hydroxyl groups for the molecule as developing photosensitizers, which were conjugated with docosahaxaenoic acid (DHA) and oleic acid (OA) by esterification reaction DCC-mediated, respectively, and gave in enough yield. Our selected PSs were obtained according to Tamiaki et al.1 and Smith et al.2 reported. Novel MPPd-DHA, MPPd-OA, PPa-N-He-DHA, and PPa-N-He-OA were prepared and structure of them was confirmed by spectroscopy's methods (1D and 2D NMR, UV-vis, and MS). The spectrum data of the compounds was clear and easy to characterize. Our synthesized chlorin-based fatty acid conjugates that could be present a synergistic effect for PDT through a more accumulation of the conjugates on tumor cells due to both of those produce a reactive oxygen substrate (ROS). The conjugates have a high lipophilicity because the UFAs were linked to the PSs and the lipophilicity of PS has proven to be an important factor because it influences the biodistribution and clearance and thus the bioactivity of drugs.