1 research outputs found
Reversible Dimerization of Polymeric Amphiphiles Acts as a Molecular Switch of Enzymatic Degradability
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