title: Targeted decationized polyplexes for cell specific gene delivery.
abstract: Decationized polyplexes have previously shown unique features, especially regarding their excellent cytocompatibility and very low degree of nonspecific cellular uptake. In the present study, targeted disulfide cross-linked decationized polyplexes were composed of a core of disulfide cross-linked poly(hydroxypropyl methacrylamide) (pHPMA) stably entrapping plasmid DNA (pDNA) and a shell of poly(ethylene glycol) (PEG) decorated with folate molecules. Folate was used as targeting ligand because of its high binding affinity to its receptor, which is overexpressed in many tumors. Studies using folate receptor overexpressing cell lines (HeLa and OVCAR-3) showed significantly higher cell uptake for the folate-targeted decationized polyplexes, when compared to their nontargeted counterparts. On the contrary, for a nonexpressing folate receptor cell line (A549) similar uptake was observed for both targeted and nontargeted decationized polyplexes. Transfection studies using OVCAR-3 cells showed higher transfection efficiency for folate-targeted polyplexes, because of improved cellular uptake. Simultaneously, introduction of targeting moiety on polyplexes did not affect their good cytocompatibilty. The results reported in this paper demonstrate that coupling of folate to decationized polyplexes generates a potential system for targeted gene delivery.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.
authors.forename: Luís
authors.initials: L
authors.lastname: Novo
authors.forename: Enrico
authors.initials: E
authors.lastname: Mastrobattista
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000178:Acrylamides / Q000737:chemistry* / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D058972:Folic Acid Transporters / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010957:Plasmids / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000178:Acrylamides; D004220:Disulfides; D058972:Folic Acid Transporters; D011092:Polyethylene Glycols; D005492:Folic Acid; C032976:N-(2-hydroxypropyl)methacrylamide