10.1021/ja510085s.s001
Ido Rosenbaum
Ido
Rosenbaum
Assaf J. Harnoy
Assaf J.
Harnoy
Einat Tirosh
Einat
Tirosh
Marina Buzhor
Marina
Buzhor
Merav Segal
Merav
Segal
Liat Frid
Liat
Frid
Rona Shaharabani
Rona
Shaharabani
Ram Avinery
Ram
Avinery
Roy Beck
Roy
Beck
Roey J. Amir
Roey J.
Amir
Encapsulation
and Covalent Binding of Molecular Payload
in Enzymatically Activated Micellar Nanocarriers
American Chemical Society
2015
loading strategy
Covalent Binding
cargo covalently encapsulated
noncovalent encapsulation
probe molecules
Enzymatically Activated Micellar NanocarriersThe
PEG
payload capacities
hybrid
enzyme
release rate
core
release rates
covalent encapsulation
micelle
Molecular Payload
encapsulated noncovalently
micellar nanocarrier
polyethylene glycol
loading capacity
type
micellar nanocarriers
amphiphilic
dendron
2015-02-18 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Encapsulation_and_Covalent_Binding_of_Molecular_Payload_in_Enzymatically_Activated_Micellar_Nanocarriers/2194936
The
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.