tetra(4-n-methylpyridyl)porphine and Urinary-Bladder-Neoplasms

DNA and porphyrin based therapeutics are important for anti-cancer treatment. The present studies demonstrate single-stranded DNA (ssDNA) assembles with meso-tetra-4-pyridyl porphine (MTP) forming porphyrin:DNA nano-complexes (PDN) that are stable in aqueous solution under physiologically relevant conditions and undergo dissociation with DNA release in hydrophobic environments, including cell membranes. PDN formation is DNA-dependent with the ratio of porphyrin:DNA being approximately two DNA nucleobases per porphyrin. PDN produce reactive oxygen species (ROS) in a light-dependent manner under conditions that favor nano-complex dissociation in the presence of hydrophobic solvents. PDN induce light-dependent cytotoxicity in vitro and anti-tumor activity towards bladder cancer xenografts in vivo. Light-dependent, PDN-mediated cell death results from ROS-mediated localized membrane damage due to lipid peroxidation with mass spectrometry indicating the generation of the lipid peroxidation products 9- and 13-hydroxy octadecanoic acid. Our results demonstrate that PDN have properties useful for therapeutic applications, including cancer treatment.. In this study, porphyrin-DNA nanocomplexes were investigated as anti-cancer therapeutics inducing ROS production in a light-dependent manner. Efficacy is demonstrated in vitro as well as a in a bladder cancer xenograft model.

Topics: Animals; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Cell Membrane; DNA, Single-Stranded; Endosomes; Female; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Peroxidation; Mice; Mice, Nude; Nanomedicine; Neoplasm Transplantation; Neoplasms; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Stearic Acids; Urinary Bladder Neoplasms