Transcript 幻灯片 1

Preparation of catechol-containing
polymers and their applications
2012.12.29
王晓莉
A Stiff Injectable Biodegradable Elastomer
Four-armed PEG modified
with dopamine is described
which changes from liquid
to elastic solid by reaction
with Fe 3 + solution.
The elastic solid can
incorporate and release
hydrophilic and
hydrophobic drugs.
1
Daniel S. Kohane, AFM, 2012, DOI: 10.1002/adfm.201202433
Catechol Redox Induced Formation of
Metal Core-Polymer Shell Nanoparticles
Ac-DOPA4-mPEG polymer
was synthetized.
The addition of Ac-DOPA4-mPEG with gold or silver ions to form
a metallic NP core with a DOPA interface and a PEG shell.
These PEG functionalized metal NPs were stable in physiological
ionic strengths and under centrifugation.
2
Phillip B. Messersmith, Chem. Mater. 2011, 23, 1130–1135
Enzymatically Degradable Mussel-Inspired
Adhesive Hydrogel
A branched PEG was modified with a DOPA-mimetic catechol
linked to the polymer backbone through an Ala-Ala dipeptide
substrate of elastase. Under oxidizing conditions, intermolecular
crosslinking of catechol groups drives rapid macromonomer
gelation.
3
Phillip B. Messersmith, Biomacromolecules 2011, 12, 4326−4334
pH responsive self-healing hydrogels formed
by boronate–catechol complexation
BDBA
4
cPEG
Under basic aqueous
conditions 1,3benzenediboronic acid
(BDBA) forms a tetrahedral
borate ester with 4-arm PEG
catechol (cPEG), giving rise
to hydrogels within 30min at
20 ℃.
The borate ester bond would
dissociate upon reduction of
the solution pH to 3.0.
Messersmith, P. B, Chem. Commun, 2011, 47 (26), 7497-7499
Catechol Polymers for pH-Responsive,
Targeted Drug Delivery to Cancer Cells
BTZ
anticancer drug
bortezomib
5
Facile conjugation of BTZ to catechol-containing PEG that are
designed to be taken up selectively by cancer cells through cell
surface receptor mediated mechanisms.
The catechol moiety was exploited for its ability to bind and release
borate containing therapeutics, such as BTZ. In acidic environments,
such as in cancer tissue, BTZ dissociates from the polymer bound
catechol groups to liberate free drug.
JACS, 2011, 133 (31), 11850-11853.
Adhesive Layer-by-Layer Films of
Carboxymethylated Cellulose NanofibrilDopamine Covalent Bioconjugates
CNFC
carboxymethylated cellulose nanofibrils
modification of CNFC with dopamine
Robust, adhesive and wet-stable
multilayer films of CNFC-DOPA
and PEI were formed and the LbL
film properties were evaluated in
terms of their structure and
adhesion characteristics.
6
ACS Nano 2012, 6 (6), 4731-4739.
Catechol-Functionalized Chitosan/ Pluronic
Hydrogels for Tissue Adhesives and Hemostatic
Catechol-conjugated chitosan
(CHI-C) and thiolated pluronic F127 (Plu-SH) were synthetized.
Chitosan conjugated with multiple catechol groups was crosslinked with terminally thiolated Pluronic F-127 triblock copolymer
at the body temperature and physiological pH to produce adhesive
sol/gel transition hydrogels.
The injectable hydrogels showed strong adhesiveness to soft tissues
and mucous layers and also demonstrated superior hemostatic
properties.
7
Lee, H,Biomacromolecules 2011, 12 (7), 2653-2659.
Hyaluronic Acid Catechol: A Biopolymer Exhibiting a
pH-Dependent Adhesive or Cohesive Property for
Human Neural Stem Cell Engineering
Basic
increase
Acidicconditions
solutions drive
HAits cohesive
property,
catechols
to be adhesive,
resulting in surface
hydrogels
coating
8
Haeshin Lee, AFM, 2012, DOI: 10.1002/adfm.201202365
Hyaluronic acid/pluronic composite hydrogels
prepared from bio-inspired catechol-thiol reaction
HA conjugated with dopamine (HA-DN) was mixed with thiol endcapped Pluronic F127 copolymer (Plu-SH) to produce a lightly crosslinked HA/Pluronic composite gel structure based on Michael-type
catechol-thiol addition reaction. The HA/ Pluronic hydrogels
exhibited temperature-dependent sol–gel phase transition behaviors.
9
Messersmith, P. B, Soft Matter 2010, 6 (5), 977-983.
Bio-inspired catechol chemistry: a new way to develop
a re-moldable and injectable coacervate hydrogel
Synthesis of dopamine conjugated
hyaluronic acid (HA-DN) and
lactose modified chitosan (chitlac).
HA-DN was employed as an
anionic polymer, chitlac was
employed as an cationic polymer.
Coacervation was achieved by both electrostatically driven
inter-polymer chain interactions as well as Michael addition
reaction of catechol molecules at alkaline pH.
10
Park, S. Y, Chemical Communications 2012, 48 (97), 11895-11897.
Mussel-Inspired Chemistry for Robust and
Surface-Modifiable Multilayer Films
PAA-dopamine/PAH
multilayer films exhibit high
reactivity with amine and
catechol, thus endowing the
chemical covalence and
retaining the assembled
morphology of
multilayer films.
Thiol-modified multilayer films with good stability were
exploited by a combination of thiols-catechol addition and then
oxidative cross-linking. The outstanding stability under harsh
conditions and the facile functionalization of the films make
them attractive for barriers, separation, and biomedical devices.
11
Jian Xu, Langmuir 2011, 27 (22), 13684-13691
Dopamine-Mediated Continuous Assembly
of Biodegradable Capsules
Dopamine-modified poly(L-glutamic acid) (PGAPDA) was used
for the continuous assembly of biodegradable capsules.
Exposure of the PGAPDA capsules to protease solution resulted
in release of encapsulated lysozyme.
12
Caruso, F, Chem.Mater, 2011, 23 (13), 3141-3143.
Enhancement of Blood Compatibility of
Poly(urethane) Substrates by Mussel-Inspired
Adhesive Heparin Coating
Heparin was modified with dopamine,
The dopamine modified heparin-coated
poly(urethane) substrate showed
significant inhibition of blood
coagulation and platelet adhesion.
13
Lee, H, Bioconjugate Chemistry 2011, 22 (7), 1264-1269.
Catechol-Modified Polyions in LbL Assembly to
Enhance Stability and Sustain Release of Biomolecules
Stability of LbL films
composing BPEI and
PAA without and with
catechol modifications
was compared.
The incorporation of catechol groups into polyelectrolytes lead to
a doubling of the average film thickness and linear film growth,
control the phenomenon of interlayer diffusion, enhance LbL film
stabilities, and achieve a sustained release of radiolabeled
biomolecules.
14
Substrate-Independent Layer-by-Layer Assembly
by Using Mussel-Adhesive-Inspired Polymers
Cationic polymer: catechol-functionalized PEI (PEI-C)
Anionic polymer: HA-catechol
Substrate independent
LbL assembly with PEI-C
and HA-catechol was
performed on PE, PET,
PTFE and PC.
The strategy avoids the
need for chemical or
physical pre-treatment
normally required for LbL
on challenging substrates
such as neutral and
hydrophobic polymers.
15
Messersmith, P. B, AM, 2008, 20 (9), 1619-1623
Polymer Composition and Substrate Influences
on the Adhesive Bonding of a Biomimetic, CrossLinking Polymer
Synthesis of Poly[(3,4-dihydroxystyrene)-co-styrene]
Adhesive bonding of poly[(3,4-dihydroxystyrene)-co-styrene] may
be the strongest of reported mussel protein mimics.
Lee, H, Bioconjugate Chemistry 2011, 22 (7), 1264-1269.
Doubly Biomimetic Catecholic Phosphorylcholine
Copolymer: A Platform Strategy for Fabricating
Antifouling Surfaces
Synthesis route of the doubly
biomimetic copolymer PMNC
The polymer can be deposited onto a variety of substrates by dipcoating in an aqueous solution, adhering to surfaces via the catechol
functional group while at the same time forming a cell outer
membrane mimetic antifouling surface.
17
Messersmith, P. B, Macromolecular Bioscience, 2012, 12(7), 979–985
Mussel-Inspired Adhesive Binders for High-Performance
Silicon Nanoparticle Anodes in Lithium-Ion Batteries
Synthesis of catecholconjugated alginate
and catecholconjugated polyacrylic
acid (Alg-C and PAA-C)
Catechol conjugated polymer binders to pure Si and Si-graphite
composite anodes with extraordinary wetness-resistant adhesion
capability can contribute significantly to improving the capacities
and cycle lives of Si NP-based anodes while remaining
electrochemically stable at the given potentials.
18
Haeshin Lee, Adv. Mater. 2013, DOI: 10.1002/adma.201203981
Next plan
• Preparation of catechol-containing chitosan
• Preparation of catechol-containing gelatin
• Construction multienzymatic system via the
biomineralization and bioadhesion and conversion of
CO2 to methanol
原子力学显微镜
2mg/ml BSA
47nm
共聚焦显微镜
CaCO3
CAT-AlgDA
微囊
AlgDA对CAT的影响
The ellipticity slightly increased and
the negative peak at 222nm
normally associated with classic αhelix structures was blue-shifted to
220.6 nm.
10
Ellipticity(mdeg)
The addition of negatively charged
AlgDA led to an increase in the
enzyme activity by 19.8% compared
with the blank one without any
AlgDA.
Free CAT
AlgDA+CAT
0
-10
-20
-30
190
200
210
220
230
240
Wavelength(nm)
It suggested that, conjugation of AlgDA to CAT (pI 5.4) affected
the enzyme activity in a positive way. Since AlgDA were negatively
charged under neutral pH condition, the electrostatic repulsion
between AlgDA and CAT (also negatively charged) enhanced the
molecular movement of CAT, therefore, increased the enzymatic
reaction rate.
25
TOC
2mm
OH
Alginate
Catechol
Calcium
N
HO
OH
HO
N
Titanium
TOC
HO
HO
OH
HO
H
N
HN
HN
O C
O
HO HO
O
O
HO
O
COONa
O
OH
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