Non-covalent assembly of meso-tetra-4-pyridyl porphine with single-stranded DNA to form nano-sized complexes with hydrophobicity-dependent DNA release and anti-tumor activity. Nanomedicine 2014 Feb;10(2):451-61
Date
08/31/2013Pubmed ID
23988714Pubmed Central ID
PMC3946208DOI
10.1016/j.nano.2013.07.019Scopus ID
2-s2.0-84895071771 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
UNLABELLED: 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.
FROM THE CLINICAL EDITOR: 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.
Author List
Ghosh S, Ucer KB, D'Agostino R Jr, Grant K, Sirintrapun J, Thomas MJ, Hantgan R, Bharadwaj M, Gmeiner WHMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic 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
