Novel pentablock copolymers for selective gene delivery to cancer cells.
OBJECTIVE
In this study, the novel poly(diethylaminoethylmethacrylate) (PDEAEM)/Pluronic F127 pentablock copolymers were found to be able to mediate high-efficiency transfection of human epithelial ovarian carcinoma (SKOV3) cell line while showing significantly lower efficacy in human epithelial retinal (ARPE-19) cell line and Swiss Mouse Fibroblast (3T3) cell line.


METHODS
The intracellular routes of polyplexes were investigated by confocal microscopy after appropriately labeling the polymer and DNA.


RESULTS
It was found that lesser nuclear entry in the ARPE-19 cells may result in the lower efficiency of transfection. Since the SKOV3 proliferation rate was found to be much higher than that of the ARPE-19 cells, the nuclear entry of polyplexes was assumed to be correlated with the proliferation rate, and it was hypothesized that the novel pentablock copolymers could mediate gene delivery selectively in fast growing cells. The different intracellular barriers to gene transfer may also account for the observed difference of transfection efficacy.


CONCLUSIONS
Although the validity of the hypothesis that our pentablock copolymer could selectively transfect hyperproliferative cells needs further examination, this present work provides a new perspective to design targeting vectors for cancer therapies based on different characteristics among specific cell types.
Zhang
Bingqi
B
Department of Chemical and Biological Engineering, Iowa State University, 3035 Sweeney Hall, Ames, Iowa, 50014, USA.
Kanapathipillai
Mathumai
M
Bisso
Paul
P
Mallapragada
Surya
S
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D020442:Poloxamer / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection
D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; C109846:poly(2-(diethylamino)ethyl methacrylate); D020442:Poloxamer; C067297:8-aminohexylamino cAMP; D004247:DNA; D000242:Cyclic AMP