Reversible Dimerization of Polymeric Amphiphiles Acts as a Molecular Switch of Enzymatic Degradability
| Autor: | Ido Rosenbaum, Assaf J. Harnoy, Ram Avinery, Uri Hananel, Roey J. Amir, Roy Beck, Einat Tirosh, Gadi Slor |
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| Rok vydání: | 2017 |
| Předmět: |
Dendrimers
Polymers and Plastics Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Polyethylene Glycols Biomaterials Surface-Active Agents Amphiphile Materials Chemistry Organic chemistry Reactivity (chemistry) Disulfides Micelles Molecular switch Chemistry technology industry and agriculture 021001 nanoscience & nanotechnology Combinatorial chemistry 0104 chemical sciences Biocatalysis Critical micelle concentration Drug delivery Degradation (geology) 0210 nano-technology Dimerization |
| Zdroj: | Biomacromolecules. 18:3457-3468 |
| ISSN: | 1526-4602 1525-7797 |
| Popis: | Enzyme-responsive polymeric micelles have great potential as drug delivery systems due to the high selectivity and overexpression of disease-associated enzymes, which could be utilized to trigger the release of active drugs only at the target site. We previously demonstrated that enzymatic degradation rates of amphiphilic PEG-dendron hybrids could be precisely tuned by gradually increasing the hydrophobic to hydrophilic ratio. However, with the increase in hydrophobicity, the micelles rapidly became too stable and could not be degraded, as often encountered for many other amphiphilic assemblies. Here we address the challenge to balance between stability and reactivity of enzymatically degradable assemblies by utilizing reversible dimerization of diblock polymeric amphiphiles to yield jemini amphiphiles. This molecular transformation serves as a tool to control the critical micelle concentration of the amphiphiles in order to tune their micellar stability and enzymatic degradability. To demonstrate this approach, we show that simple dimerization of two polymeric amphiphiles through a single reversible disulfide bond significantly increased the stability of their micellar assemblies toward enzymatic degradation, although the hydrophilic to hydrophobic ratio was not changed. Reduction of the disulfide bond led to dedimerization of the polymeric hybrids and allowed their degradation by the activating enzyme. The generality of the approach is demonstrated by designing both esterase- and amidase-responsive micellar systems. This new molecular design can serve as a simple tool to increase the stability of polymeric micelles without impairing their enzymatic degradability. |
| Databáze: | OpenAIRE |
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