Faculty Collaboration Database

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

08/31/2013

Pubmed ID

23988714

Pubmed Central ID

PMC3946208

DOI

10.1016/j.nano.2013.07.019

Scopus ID

2-s2.0-84895071771 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

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 WH

Author

Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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