Combination of nanogel polyethylene glycol-polyethylenimine and 6(hydroxymethyl)-1,4-anthracenedione as an anticancer nanomedicine.
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.
Ganta
Chanran
C
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Shi
Aibin
A
Battina
Srinivas K
SK
Pyle
Marla
M
Rana
Sandeep
S
Hua
Duy H
DH
Tamura
Masaaki
M
Troyer
Deryl
D
D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation; D005782:Gels; D050997:Nanomedicine; D009369:Neoplasms / Q000628:therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000008:administration & dosage*; D012377:Rodentia
C530630:6(hydroxymethyl)-1,4-anthracenedione; D000880:Anthraquinones; D000970:Antineoplastic Agents; D005782:Gels; D011092:Polyethylene Glycols; D011094:Polyethyleneimine