Targeted Decationized Polyplexes for Cell Specific Gene Delivery

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 po...

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Bibliographic Details
Published in:Bioconjugate chemistry 2014-04, Vol.25 (4), p.802-812
Main Authors: Novo, Luís, Mastrobattista, Enrico, van Nostrum, Cornelus F, Hennink, Wim E
Format: Article
Language:English
Subjects:
Acrylamides - chemistry
Acrylamides - metabolism
Cells
Chemistry
Disulfides - chemistry
Drug Delivery Systems - methods
Ethylene
Folic Acid - chemistry
Folic Acid - metabolism
Folic Acid Transporters - genetics
Folic Acid Transporters - metabolism
Genes
Genetics
HeLa Cells
Humans
Molecular Structure
Molecules
Plasmids - metabolism
Polyethylene Glycols - chemistry
Polyethylene Glycols - metabolism
Transfection - methods
Tumor Cells, Cultured
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc500074a