Gene Delivery Properties of End-Modified Poly(β-amino ester)s
Identifieur interne : 002B96 ( Main/Exploration ); précédent : 002B95; suivant : 002B97Gene Delivery Properties of End-Modified Poly(β-amino ester)s
Auteurs : Gregory T. Zugates [États-Unis] ; Nathan C. Tedford [États-Unis] ; Andreas Zumbuehl [États-Unis, Suisse] ; Siddharth Jhunjhunwala [États-Unis] ; Christina S. Kang [États-Unis] ; Linda G. Griffith [États-Unis] ; Douglas A. Lauffenburger [États-Unis] ; Robert Langer [États-Unis] ; Daniel G. Anderson [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 2007.
Abstract
Here, we present the synthesis of a library of end-modified poly(β-amino ester)s and assess their utility as gene delivery vehicles. Polymers were synthesized using a rapid, two-step approach that involves initial preparation of an acrylate-terminated polymer followed by a postpolymerization amine-capping step to generate end-functionalized polymers. Using a highly efficient poly(β-amino ester), C32, we show that the terminal amine can greatly affect and improve polymer properties relevant to gene delivery. Specifically, the in vitro transfection levels can be increased by 30% and the optimal polymer:DNA ratio lowered 5-fold by conjugation of the appropriate end group. The most effective modifications were made by grafting primary diamine molecules to the chain termini. The added charge and hydrophobicity of some derivatives enhanced DNA binding and resulted in the formation of polymer–DNA complexes less than 100 nm in diameter. In addition, cellular uptake was improved 5-fold over unmodified C32. The end-modified poly(β-amino ester)s presented here are some of the most effective gene-delivery polycations, superior to polyethylenimine and previously reported poly(β-amino ester)s. These results show that the end-modification of poly(β-amino ester)s is a general strategy to alter functionality and improve the delivery performance of these materials.
Url:
DOI: 10.1021/bc7002082
Affiliations:
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Polymers were synthesized using a rapid, two-step approach that involves initial preparation of an acrylate-terminated polymer followed by a postpolymerization amine-capping step to generate end-functionalized polymers. Using a highly efficient poly(β-amino ester), C32, we show that the terminal amine can greatly affect and improve polymer properties relevant to gene delivery. Specifically, the in vitro transfection levels can be increased by 30% and the optimal polymer:DNA ratio lowered 5-fold by conjugation of the appropriate end group. The most effective modifications were made by grafting primary diamine molecules to the chain termini. The added charge and hydrophobicity of some derivatives enhanced DNA binding and resulted in the formation of polymer–DNA complexes less than 100 nm in diameter. In addition, cellular uptake was improved 5-fold over unmodified C32. The end-modified poly(β-amino ester)s presented here are some of the most effective gene-delivery polycations, superior to polyethylenimine and previously reported poly(β-amino ester)s. These results show that the end-modification of poly(β-amino ester)s is a general strategy to alter functionality and improve the delivery performance of these materials.</div></front></TEI><affiliations><list><country><li>Suisse</li><li>États-Unis</li></country><region><li>Massachusetts</li><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Zugates, Gregory T" sort="Zugates, Gregory T" uniqKey="Zugates G" first="Gregory T." last="Zugates">Gregory T. Zugates</name></region><name sortKey="Anderson, Daniel G" sort="Anderson, Daniel G" uniqKey="Anderson D" first="Daniel G." last="Anderson">Daniel G. Anderson</name><name sortKey="Anderson, Daniel G" sort="Anderson, Daniel G" uniqKey="Anderson D" first="Daniel G." last="Anderson">Daniel G. Anderson</name><name sortKey="Griffith, Linda G" sort="Griffith, Linda G" uniqKey="Griffith L" first="Linda G." last="Griffith">Linda G. Griffith</name><name sortKey="Jhunjhunwala, Siddharth" sort="Jhunjhunwala, Siddharth" uniqKey="Jhunjhunwala S" first="Siddharth" last="Jhunjhunwala">Siddharth Jhunjhunwala</name><name sortKey="Jhunjhunwala, Siddharth" sort="Jhunjhunwala, Siddharth" uniqKey="Jhunjhunwala S" first="Siddharth" last="Jhunjhunwala">Siddharth Jhunjhunwala</name><name sortKey="Kang, Christina S" sort="Kang, Christina S" uniqKey="Kang C" first="Christina S." last="Kang">Christina S. Kang</name><name sortKey="Langer, Robert" sort="Langer, Robert" uniqKey="Langer R" first="Robert" last="Langer">Robert Langer</name><name sortKey="Lauffenburger, Douglas A" sort="Lauffenburger, Douglas A" uniqKey="Lauffenburger D" first="Douglas A." last="Lauffenburger">Douglas A. Lauffenburger</name><name sortKey="Tedford, Nathan C" sort="Tedford, Nathan C" uniqKey="Tedford N" first="Nathan C." last="Tedford">Nathan C. Tedford</name><name sortKey="Zumbuehl, Andreas" sort="Zumbuehl, Andreas" uniqKey="Zumbuehl A" first="Andreas" last="Zumbuehl">Andreas Zumbuehl</name></country><country name="Suisse"><noRegion><name sortKey="Zumbuehl, Andreas" sort="Zumbuehl, Andreas" uniqKey="Zumbuehl A" first="Andreas" last="Zumbuehl">Andreas Zumbuehl</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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