3 research outputs found
Scavenging ROS: Superoxide Dismutase/Catalase Mimetics by the Use of an Oxidation-Sensitive Nanocarrier/Enzyme Conjugate
Reactive Oxygen Species (ROS) are quintessential inflammatory
compounds
with oxidizing behavior. We have successfully developed a micellar
system with responsiveness at the same time to two of the most important
ROS: superoxide and hydrogen peroxide. This allows for an effective
and selective capture of the two compounds and, in perspective, for
inflammation-responsive drug release. The system is composed of superoxide
dismutase (SOD) conjugated to oxidation-sensitive amphiphilic polysulfide/PEG
block copolymers; the conjugate combines the SOD reactivity toward
superoxide with that of hydrophobic thioethers toward hydrogen peroxide.
Specifically, here we have demonstrated how this hybrid system can
efficiently convert superoxide into hydrogen peroxide, which is then
“mopped-up” by the polysulfides: this <i>modus
operandi</i> is functionally analogous to the SOD/catalase combination,
with the advantages of (a) being based on a single and more stable
system, and (b) a higher overall efficiency due the physical proximity
of the two ROS-reactive centers (SOD and polysulfides)
PEGylation of Nanosubstrates (Titania) with Multifunctional Reagents: At the Crossroads between Nanoparticles and Nanocomposites
Titania (anatase) nanoparticles were successfully PEGylated
through
the use of catechol (dopamine)-terminated PEG derivatives. The resulting
materials were characterized by excellent stability at neutral pH
and extremely low toxicity (phagocytic and nonphagocytic cell lines).
In
particular, we focused on the comparison between mono- and bis-catechol
PEGs. Due to the double terminal anchorage on the titania surface,
bis-catechol ligands can produce chains differing from classical monoanchored
PEG in conformation (horseshoe-shaped vs brush) and thus the possibility
of interactions with biomolecules. At the same time, less than quantitative
catechol binding may lead to the presence of dangling chains with
unbound catechols which can polymerize and eventually produce PEG/titania
nanocomposite colloids. Our results on double-functional PEG2000 show
the latter to be the case. Pluronic F127 was also used as a bifunctional
ligand, leading to nanocomposite aggregates with an even larger organic
content
Tyrosinase-Mediated Bioconjugation. A Versatile Approach to Chimeric Macromolecules
We
present a method for tyrosine-selective and reversible bioconjugation;
tyrosines are enzymatically converted into catechols and in situ “clicked”
onto boronic acids. Importantly, our process selectively produces
catechols and avoids quinones, thereby improving the control over
the chemical identity of the products. We have conjugated boronic
acid-containing hyaluronic acid (HyA) to peptides bearing tyrosines
in variable number and position; the use of tagging peptides for the
provision of well exposed tyrosine residuesî—¸in our case the
hemagglutinin-derived HA-tagî—¸makes our approach applicable
to virtually any protein; we have demonstrated this concept by conjugating
HA-tagged ovalbumin to HyA, thereby also showing the feasibility of
producing chimeric proteoglycans. A caveat of this appproach is that,
although the formation of boronic esters does not affect the biological
recognition of substrates (ovalbumin and HyA), the introduction of
catechols may alter some of their biological properties: for example,
only after tyrosinase treatment ovalbumin directly induced dendritic
cell maturation, either alone or as a HyA conjugate