Trehalose Click Polymers Inhibit Nanoparticle Aggregation and Promote pDNA Delivery in Serum
| Autor: | Guodong Zhang, Yemin Liu, Theresa M. Reineke, Lisa E. Prevette, Sathya Srinivasachari |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Serum
Biocompatibility Cell Survival Polymers Biochemistry Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Genes Reporter Humans Moiety Organic chemistry Particle Size Hexoses chemistry.chemical_classification Drug Carriers Molecular Structure Chemistry Gene Transfer Techniques Trehalose DNA General Chemistry Polymer Combinatorial chemistry Monomer Polymerization Nucleic acid Nanoparticles Amine gas treating HeLa Cells |
| Zdroj: | Journal of the American Chemical Society. 128:8176-8184 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja0585580 |
| Popis: | Herein, three new glycopolymers have been synthesized via "click polymerization" to promote nucleic acid delivery in the presence of biological media containing serum. These structures were designed to contain a trehalose moiety to promote biocompatibility, water solubility, and stability against aggregation, amide-triazole groups to enhance DNA binding affinity, and an oligoamine unit to facilitate DNA encapsulation, phosphate neutralization, and interactions with cell surfaces. A 2,3,4,2',3',4'-hexa-O-acetyl-6,6'-diazido-6,6'-dideoxy-D-trehalose (4) monomer was polymerized via copper(I)-catalyzed azide-alkyne cycloaddition with a series of dialkyne-amide comonomers that contain either one, two, or three Boc-protected secondary amines (7a, 7b, or 7c, respectively). After deprotection, three water-soluble polycations (9a, 9b, or 9c) were obtained with similar degrees of polymerization (n = 56-61) to elucidate the role of amine number on nucleic acid binding, complex formation, stability, and cellular delivery. Gel electrophoresis and ethidium bromide experiments showed that 9a-9c associated with plasmid DNA (pDNA) and formed complexes (polyplexes) at N/P ratios dependent on the amine number. TEM experiments revealed that 9a-9c polyplexes were small (50-120 nm) and had morphologies (spherical and rodlike) associated with the polymer chain stiffness. Dynamic light scattering studies in the presence of media containing serum demonstrated that 9c polyplexes had a low degree of flocculation, whereas 9a and 9b polyplexesd aggregate rapidly. Further biological studies revealed that these structures were biocompatible and deliver pDNA into HeLa cells. Particularly, 9c polyplexes promoted high delivery efficacy and gene expression profiles in the presence of serum. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|