Bacterial Resistance and Prostate Cancer Susceptibility Toward Metal-Ion-doped DNA Complexes

ACS Appl Mater Interfaces. 2018 Dec 26;10(51):44290-44300. doi: 10.1021/acsami.8b17013. Epub 2018 Dec 14.

Abstract

DNA nanotechnology has laid a platform to construct a variety of custom-shaped nanoscale objects for functionalization of specific target materials to achieve programmability and molecular recognition. Herein, we prepared DNA nanostructures [namely, synthetic DNA rings (RDNA) and DNA duplexes extracted from salmon (SDNA)] containing metal ions (M2+) such as Cu2+, Ni2+, and Zn2+ as payloads for delivery to exterminate highly pathologic hospital bacterial strains (e.g., Escherichia coli and Bacillus subtilis) and prostate cancer cells (i.e., PC3, LNCaP, TRAMP-C1, 22Rv1, and DU145). Morphologies of these M2+-doped RDNA were visualized using atomic force microscopy. Interactions between M2+ and DNA were studied using UV-vis and Fourier transform infrared spectroscopy. Quantitative composition and chemical changes in DNA without or with M2+ were obtained using X-ray photoelectron spectroscopy. In addition, M2+-doped DNA complexes were subjected to antibacterial activity studies. They showed no bacteriostatic or bactericidal effects on bacterial strains used. Finally, in vitro cellular toxicity study was conducted to evaluate the effect of pristine DNA and M2+-doped DNA complexes on prostate cancer cells. Cytotoxicities conferred by M2+-doped DNA complexes for most cell lines were significantly higher than those of M2+ without DNA. Cellular uptake of these complexes was confirmed by fluorescence microscopy using PhenGreen FL indicator. On the basis of our observations, DNA nanostructures can be used as safe and efficient nanocarriers for delivery of therapeutics. They have enhanced therapeutic window than bare metals.

Keywords: DNA; bacterial resistance; metal-ion-doped DNA; prostate cancer; spectroscopy.

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bacillus subtilis / growth & development*
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • DNA* / chemistry
  • DNA* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • Drug Resistance, Bacterial / drug effects*
  • Escherichia coli / growth & development*
  • Humans
  • Male
  • Nanostructures* / chemistry
  • Nanostructures* / therapeutic use
  • PC-3 Cells
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology

Substances

  • Anti-Bacterial Agents
  • Coordination Complexes
  • Drug Carriers
  • DNA