Alkyl sulfonyl derivatized PAMAM-G2dendrimers as nonviral gene delivery vectors with improved transfection efficiencies
| Autor: | Fernando Hernandez Mateo, FRANCISCO SANTOYO-GONZALEZ, Alicia Megía Fernández, Julia Morales Sanfrutos, Alicia Megia-Fernandez, Maria D Giron, Julia Isabel Morales Sanfrutos |
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| Rok vydání: | 2011 |
| Předmět: |
Dendrimers
Alkylation Cell Survival Stereochemistry Genetic Vectors Gene delivery Biochemistry Cell Line Mice chemistry.chemical_compound Cricetinae Dendrimer Amphiphile Animals Sulfones Physical and Theoretical Chemistry Alkyl Sulfonyl chemistry.chemical_classification Molecular Structure Chemistry Organic Chemistry Gene Transfer Techniques Transfection Combinatorial chemistry DNA |
| Zdroj: | Org. Biomol. Chem.. 9:851-864 |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | Amphiphilic dendrimer-based gene delivery vectors bearing peripheral alkyl sulfonyl hydrophobic tails were constructed using low-generation PAMAM-G2 as the core and functionalized by means of the aza-Michael type addition of its primary amino groups to vinylsulfone derivatives as an efficient tool for surface engineering. While the unmodified PAMAM-G2 was unable to efficiently transfect eukaryotic cells, functionalized PAMAM-G2 dendrimers were able to bind DNA at low N/P ratios, protect DNA from digestion with DNase I and showed high transfection efficiencies and low cytotoxicity. Dendrimers with a C18 alkyl chain produced transfection efficiencies up to 3.1 fold higher than LipofectAMINE™ 2000 in CHO-k1 cells. The dendriplexes based in functionalized PAMAM-G2 also showed the ability to retain their transfection properties in the presence of serum and the ability to transfect different eukaryotic cell lines such as Neuro-2A and RAW 264.7. Taking advantage of the vinylsulfone chemistry, fluorescent PAMAM-G2 derivatives of these vectors were prepared as molecular probes to determine cellular uptake and internalization through a clathrin-independent mechanism. |
| Databáze: | OpenAIRE |
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