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Encapsulation and Covalent Binding of Molecular Payload in Enzymatically Activated Micellar Nanocarriers
journal contribution
posted on 2015-02-18, 00:00 authored by Ido Rosenbaum, Assaf J. Harnoy, Einat Tirosh, Marina Buzhor, Merav Segal, Liat Frid, Rona Shaharabani, Ram Avinery, Roy Beck, Roey J. AmirThe
high selectivity and often-observed overexpression of specific
disease-associated enzymes make them extremely attractive for triggering
the release of hydrophobic drug or probe molecules from stimuli-responsive
micellar nanocarriers. Here we utilized highly modular amphiphilic
polymeric hybrids, composed of a linear hydrophilic polyethylene glycol
(PEG) and an esterase-responsive hydrophobic dendron, to prepare and
study two diverse strategies for loading of enzyme-responsive micelles.
In the first type of micelles, hydrophobic coumarin-derived dyes were
encapsulated noncovalently inside the hydrophobic core of the micelle,
which was composed of lipophilic enzyme-responsive dendrons. In the
second type of micellar nanocarrier the hydrophobic molecular cargo
was covalently linked to the end-groups of the dendron through enzyme-cleavable
bonds. These amphiphilic hybrids self-assembled into micellar nanocarriers
with their cargo covalently encapsulated within the hydrophobic core.
Both types of micelles were highly responsive toward the activating
enzyme and released their molecular cargo upon enzymatic stimulus.
Importantly, while faster release was observed with noncovalent encapsulation,
higher loading capacity and slower release rate were achieved with
covalent encapsulation. Our results clearly indicate the great potential
of enzyme-responsive micellar delivery platforms due to the ability
to tune their payload capacities and release rates by adjusting the
loading strategy.
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loading strategyCovalent Bindingcargo covalently encapsulatednoncovalent encapsulationprobe moleculesEnzymatically Activated Micellar NanocarriersThePEGpayload capacitieshybridenzymerelease ratecorerelease ratescovalent encapsulationmicelleMolecular Payloadencapsulated noncovalentlymicellar nanocarrierpolyethylene glycolloading capacitytypemicellar nanocarriersamphiphilicdendron
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