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.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Chanran
C
Ganta
Aibin
A
Shi
Srinivas K
SK
Battina
Marla
M
Pyle
Sandeep
S
Rana
Duy H
DH
Hua
Masaaki
M
Tamura
Deryl
D
Troyer
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