Combination of Nanogel Polyethylene glycol-Polyethylenimine and 6 (hydroxymethyl)-14-anthracenedione as an Anticancer Nanomedicine

摘要

Nanoparticles have many potential applications. Polyethylene glycol-polyethylenimine (PEG-PEI) nanogels have been used to deliver nucleic acids and oligonucleotides into cells. We first synthesized various nanogels with altering ratios of CH2O:CH2N (methylene protons) in PEG-PEI and tested their cytotoxicity using a rodent pancreatic adenocarcinoma cell line (Pan 02). Results indicate that the nanogel PEG-PEI with lower methylene protons ratio (4:1) exhibited a strong cytotoxicity over the higher methylene protons ratio (~6.8:1). We then incorporated a newly synthesized anti-cancer drug, 6-(hydroxymethyl)-1,4-anthracenedione (AQ) analogue (AQ10) into nanogel PEG-PEI with higher methylene protons ratio (~6.8:1) and tested the effect of AQ10 encapsulated nanogel PEG-PEI (AQ10-nanogel PEG-PEI) and AQ10 dissolved in DMSO on Pan 02 cell growth. Our results showed that, Pan 02 cells treated with AQ10-nanogel PEG-PEI was three to four times more effective in cell growth attenuation than the cells treated with AQ10 alone. Nanogel PEG-PEI apparently acts as a drug delivery agent by penetrating the cell membrane and carrying the anti-cancer drug AQ10 into the cells, so that they become more susceptible to the drug even at a lower dose. These results suggest that AQ10-nanogel PEG-PEI is a potentially effective anti-cancer agent in pancreatic cancer therapy.