Cart
Article
Trehalose Click Polymers Inhibit Nanoparticle Aggregation and Promote pDNA Delivery in Serum
Full Text HTML
Hi-Res PDFPurchase the full-text
- PDF/HTML,
figures/images,
references and tables,
(where available)
Section:Abstract
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.
Citing Articles
Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 36 ACS Journal articles (5 most recent appear below).
β-Cyclodextrin-Based Polycationic Amphiphilic “Click” Clusters: Effect of Structural Modifications in Their DNA Complexing and Delivery Properties
Alejandro Méndez-Ardoy, Nicolas Guilloteau, Christophe Di Giorgio, Pierre Vierling, Francisco Santoyo-González, Carmen Ortiz Mellet, and José M. García FernándezThe Journal of Organic Chemistry2011 76 (15), 5882-5894β-Cyclodextrin-Based Polycationic Amphiphilic “Click” Clusters: Effect of Structural Modifications in Their DNA Complexing and Delivery Properties
Alejandro Méndez-Ardoy, Nicolas Guilloteau, Christophe Di Giorgio, Pierre Vierling, Francisco Santoyo-González, Carmen Ortiz Mellet, and José M. García FernándezThe Journal of Organic Chemistry2011 76 (15), 5882-5894Monodisperse facial amphiphiles consisting of a β-cyclodextrin (βCD) platform exposing a multivalent display of cationic groups at the primary rim and bearing hydrophobic chains at the secondary oxygens have been prepared by implementing two very robust “...
Nucleic Acid Carriers Based on Precise Polymer Conjugates
Christina Troiber and Ernst WagnerBioconjugate Chemistry2011 Article ASAPNucleic Acid Carriers Based on Precise Polymer Conjugates
Christina Troiber and Ernst WagnerBioconjugate Chemistry2011 Article ASAPPolymer polydispersity, random conjugation of functional groups, and poorly understood structure–activity relationships have constantly hampered progress in the development of nucleic acid carriers. This review focuses on the synthetic concepts for the ...
Synthesis and Postpolymerization Functionalization of Poly(5-iodo-1,2,3-triazole)s
Erik Schwartz, Kurt Breitenkamp, and Valery V. FokinMacromolecules2011 44 (12), 4735-4741Synthesis and Postpolymerization Functionalization of Poly(5-iodo-1,2,3-triazole)s
Erik Schwartz, Kurt Breitenkamp, and Valery V. FokinMacromolecules2011 44 (12), 4735-4741The step-growth, click polymerization of complementary azide and alkyne-containing monomers to produce polytriazoles (PTAs) has become a versatile and popular method of preparing structurally diverse high molecular weight polymers with a variety of useful ...
Linear Cationic Click Polymers/DNA Nanoparticles: In Vitro Structure–Activity Relationship and In Vivo Evaluation for Gene Delivery
Yu Gao, Qi Yin, Lingli Chen, Zhiwen Zhang, and Yaping LiBioconjugate Chemistry2011 22 (6), 1153-1161Linear Cationic Click Polymers/DNA Nanoparticles: In Vitro Structure–Activity Relationship and In Vivo Evaluation for Gene Delivery
Yu Gao, Qi Yin, Lingli Chen, Zhiwen Zhang, and Yaping LiBioconjugate Chemistry2011 22 (6), 1153-1161The aim of this work was to explore the structure–activity relationships (SAR) of a series of novel linear cationic click polymers with various structures for in vitro gene delivery and in vivo gene transfer. The experimental results revealed that the ...
Structure–Activity Examination of Poly(glycoamidoguanidine)s: Glycopolycations Containing Guanidine Units for Nucleic Acid Delivery
Vijay P. Taori, Hao Lu, and Theresa M. ReinekeBiomacromolecules2011 12 (6), 2055-2063Structure–Activity Examination of Poly(glycoamidoguanidine)s: Glycopolycations Containing Guanidine Units for Nucleic Acid Delivery
Vijay P. Taori, Hao Lu, and Theresa M. ReinekeBiomacromolecules2011 12 (6), 2055-2063In this study we synthesized a new series of polymers known as poly(glycoamidoguanidine)s (PGAGs). These new polymer structures were synthesized by copolymerizing a carbohydrate monomer (diester; galatarate or tartarate) with a diamine incorporating ...
Tools
-
Add to Favorites
-
Download Citation
-
Email a Colleague -
Permalink
Order Reprints
Rights & Permissions
Citation Alerts
History
- Published In Issue June 28, 2006
- Received December 28, 2005
ACS
Network
Facebook
Tweet This
CiteULike
Newsvine
Digg This
Delicious
