In Vitro Gene Delivery by Degraded Polyamidoamine Dendrimers
| Autor: | Carl T. Redemann, Francis C. Szoka, Mary Tang |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Models
Molecular Hot Temperature Polymers Genetic Vectors Population Biomedical Engineering Pharmaceutical Science Bioengineering Gene delivery Transfection Branching (polymer chemistry) Drug Delivery Systems Dendrimer Organic chemistry Reduced viscosity education Pharmacology chemistry.chemical_classification education.field_of_study Viscosity Organic Chemistry Cationic polymerization DNA Polymer Hydrogen-Ion Concentration Solutions Microscopy Electron chemistry Biophysics Plasmids Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 7:703-714 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc9600630 |
| Popis: | Transfection of cultured cells has been reported using complexes between DNA and spherical cationic polyamidoamine polymers (Starburst dendrimers) that consist of primary amines on the surface and tertiary amines in the interior. The transfection activity of the dendrimers is dramatically enhanced (> 50-fold) by heat treatment in a variety of solvolytic solvents, e.g., water or butanol. Such treatment induces significant degradation of the dendrimer at the amide linkage, resulting in a heterodisperse population of compounds with molecular weights ranging from the very low (< 1500 Da) to several tens of kilodaltons. The compound facilitating transfection is the high molecular weight component of the degraded product and is denoted as a "fractured" dendrimer. Transfection activity is related both to the initial size of the dendrimer and its degree of degradation. Fractured dendrimers exhibit an increased apparent volume change as measured by an increase in the reduced viscosity upon protonation of the terminal amines as pH is reduced from 10.5 to 7.2 whereas intact dendrimers do not. Dendrimers with defective branching have been synthesized and also have improved transfection activity compared to that of the intact dendrimers. For a series of heat-treated dendrimers we observe a correlation between transfection activity and the degree of flexibility, computed with a random cleavage simulation of the degradation process. We suggest that the increased transfection after the heating process is principally due to the increase in flexibility that enables the fractured dendrimer to be compact when complexed with DNA and swell when released from DNA. |
| Databáze: | OpenAIRE |
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