Combination of nanogel polyethylene glycol-polyethylenimine and 6(hydroxymethyl)-1,4-anthracenedione as an anticancer nanomedicine

J Nanosci Nanotechnol. 2008 May;8(5):2334-40. doi: 10.1166/jnn.2008.294.

Abstract

Polyethylene glycol-polyethylenimine (PEG-PEI) nanogels have been used to deliver nucleic acids and oligonucleotides into cells. First, we synthesized PEG-PEI nanogels with methylene proton ratios (CH2O:CH2N) in PEG-PEI ranging from approximately 6.8:1 to 4:1 and less, as shown by 1H NMR spectra. We first synthesized various nanogels with varying ratios of CH2O:CH2N (methylene proton) in PEG-PEI as shown by 1H NMR spectra and tested their cytotoxicity using a rodent pancreatic adenocarcinoma cell line (Pan 02). We showed that the nanogel PEG-PEI with methylene proton ratio of 4:1 was strongly cytotoxic to Pan 02 cells in vitro, while the nanogel with the methylene proton ratio of 6.8:1 was not toxic. We incorporated a novel anti-cancer drug, 6-(hydroxymethyl)-1,4-anthracenedione (AQ) analogue (AQ10) into nontoxic nanogel PEG-PEI and tested the effect of AQ10 loaded nanogel PEG-PEI (AQ10-nanogel PEG-PEI) and AQ10 dissolved in DMSO on Pan 02 cell growth. The size of this AQ10-nanogel PEG-PEI was characterized using atomic force microscopy (AFM). Our studies showed that the AQ10-nanogel PEG-PEI is readily taken up by Pan 02 cells. Growth attenuation of Pan 02 cells treated with AQ10-nanogel PEG-PEI was three to four times that of cells treated with AQ10 dissolved in DMSO. These results suggest that PEG-PEI, usually used to deliver nucleic acids into cells, can also be used to deliver an insoluble small molecule anticancer drug, AQ10.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anthraquinones / administration & dosage*
  • Antineoplastic Agents / administration & dosage*
  • Cell Proliferation
  • Gels
  • Nanomedicine*
  • Neoplasms / therapy*
  • Polyethylene Glycols / administration & dosage*
  • Polyethyleneimine / administration & dosage*
  • Rodentia

Substances

  • 6(hydroxymethyl)-1,4-anthracenedione
  • Anthraquinones
  • Antineoplastic Agents
  • Gels
  • Polyethylene Glycols
  • Polyethyleneimine