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Nanomedicine. 2014 Feb;10(2):451-61. doi: 10.1016/j.nano.2013.07.019. Epub 2013 Aug 27.

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.

Author information

  • 1Program in Molecular Genetics, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • 2Department of Physics, Wake Forest University, Winston-Salem, NC, USA.
  • 3Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • 4Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • 5Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • 6Department of Genrontology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • 7Program in Molecular Genetics, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: bgmeiner@wakehealth.edu.

Abstract

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.

© 2014.

KEYWORDS:

Cancer therapy; Multi-modality nanoparticle; Photodynamic therapy; Porphyrin: DNA assembly

PMID:
23988714
[PubMed - in process]
PMCID:
PMC3946208
Free PMC Article

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