Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers
| Autor: | Bahar Demirdirek, Prabhas V. Moghe, Nicole M. Iverson, Sarah M. Sparks, Kathryn E. Uhrich |
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| Rok vydání: | 2009 |
| Předmět: |
Anions
Materials science Rotation Stereochemistry Polymers Carboxylic acid media_common.quotation_subject Biomedical Engineering Carboxylic Acids Conjugated system Biochemistry Article Cell Line Polyethylene Glycols Biomaterials chemistry.chemical_compound Structure-Activity Relationship Amphiphile PEG ratio Humans Particle Size Internalization Molecular Biology media_common chemistry.chemical_classification Macrophages General Medicine Nuclear magnetic resonance spectroscopy Endocytosis Nanostructures Lipoproteins LDL chemistry Biophysics Ethylene glycol Hydrophobic and Hydrophilic Interactions Biotechnology Macromolecule |
| Zdroj: | Acta biomaterialia. 6(8) |
| ISSN: | 1878-7568 |
| Popis: | A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure-activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules. |
| Databáze: | OpenAIRE |
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