Preparation of catechol-containing

polymers and their applications

2012.12.29王晓莉

A Stiff Injectable Biodegradable ElastomerA Stiff Injectable Biodegradable Elastomer

Daniel S. Kohane, AFM, 2012, DOI: 10.1002/adfm.201202433

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

Catechol Redox Induced Formation of Metal Core-Polymer Shell Nanoparticles

Catechol Redox Induced Formation of Metal Core-Polymer Shell Nanoparticles

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.

Phillip B. Messersmith, Chem. Mater. 2011, 23, 1130–1135

Ac-DOPA4-mPEG polymer was synthetized.

2

Enzymatically Degradable Mussel-Inspired Adhesive Hydrogel

Enzymatically Degradable Mussel-Inspired Adhesive Hydrogel

Phillip B. Messersmith, Biomacromolecules 2011, 12, 4326−4334

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

pH responsive self-healing hydrogels formed by boronate–catechol complexation

pH responsive self-healing hydrogels formed by boronate–catechol complexation

Under basic aqueous conditions 1,3-benzenediboronic 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.

BDBA cPEG

4

Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells

Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells

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.

BTZ anticancer drug bortezomib

JACS, 2011, 133 (31), 11850-11853.5

Adhesive Layer-by-Layer Films of Carboxymethylated Cellulose Nanofibril-Dopamine Covalent Bioconjugates

Adhesive Layer-by-Layer Films of Carboxymethylated Cellulose Nanofibril-Dopamine Covalent Bioconjugates CNFC

carboxymethylated cellulose nanofibrils

Robust, adhesive and wet-stable multilayer films of CNFC-DOPAand PEI were formed and the LbL film properties were evaluated in terms of their structure andadhesion characteristics.

modification of CNFC with dopamine

ACS Nano 2012, 6 (6), 4731-4739.6

Catechol-Functionalized Chitosan/ Pluronic Hydrogels for Tissue Adhesives and Hemostatic

Catechol-Functionalized Chitosan/ Pluronic Hydrogels for Tissue Adhesives and Hemostatic

Chitosan conjugated with multiple catechol groups was cross-linked 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.

Catechol-conjugated chitosan (CHI-C) and thiolated pluronic F-127 (Plu-SH) were synthetized.

Lee, H,Biomacromolecules 2011, 12 (7), 2653-2659.7

Hyaluronic Acid Catechol: A Biopolymer Exhibiting apH-Dependent Adhesive or Cohesive Property for Human Neural Stem Cell Engineering

Hyaluronic Acid Catechol: A Biopolymer Exhibiting apH-Dependent Adhesive or Cohesive Property for Human Neural Stem Cell Engineering

Basic conditions increase its cohesive property, resulting in hydrogels

Acidic solutions drive HA-catechols to be adhesive, resulting in surface coating

Haeshin Lee, AFM, 2012, DOI: 10.1002/adfm.2012023658

Hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired

catechol-thiol reaction

Hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired

catechol-thiol reaction

HA conjugated with dopamine (HA-DN) was mixed with thiol end-capped Pluronic F127 copolymer (Plu-SH) to produce a lightly cross-linked 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.

Messersmith, P. B, Soft Matter 2010, 6 (5), 977-983.9

Bio-inspired catechol chemistry: a new way to develop a re-moldable and injectable coacervate hydrogel

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.

Park, S. Y, Chemical Communications 2012, 48 (97), 11895-11897.10

Mussel-Inspired Chemistry for Robust and Surface-Modifiable Multilayer Films

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 ofmultilayer films.

Thiol-modified multilayer films with good stability wereexploited by a combination of thiols-catechol addition and then oxidative cross-linking. The outstanding stability under harshconditions and the facile functionalization of the films make them attractive for barriers, separation, and biomedical devices.

Jian Xu, Langmuir 2011, 27 (22), 13684-13691.11

Dopamine-Mediated Continuous Assembly of Biodegradable Capsules

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.

Caruso, F, Chem.Mater, 2011, 23 (13), 3141-3143.12

Enhancement of Blood Compatibility of Poly(urethane) Substrates by Mussel-Inspired Adhesive Heparin Coating

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.

Lee, H, Bioconjugate Chemistry 2011, 22 (7), 1264-1269.13

Catechol-Modified Polyions in LbL Assembly to Enhance Stability and Sustain

Release of Biomolecules

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.

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Substrate-Independent Layer-by-Layer Assembly by Using Mussel-Adhesive-Inspired Polymers

Substrate-Independent Layer-by-Layer Assembly by Using Mussel-Adhesive-Inspired Polymers

Cationic polymer: catechol-functionalized PEI (PEI-C)Anionic polymer: HA-catechol

Messersmith, P. B, AM, 2008, 20 (9), 1619-1623.

Substrate independentLbL 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

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.

Polymer Composition and Substrate Influences on the Adhesive Bonding of a Biomimetic, Cross-Linking Polymer

Polymer Composition and Substrate Influences on the Adhesive Bonding of a Biomimetic, Cross-Linking Polymer

Doubly Biomimetic Catecholic Phosphorylcholine Copolymer: A Platform Strategy for Fabricating Antifouling Surfaces

Doubly Biomimetic Catecholic Phosphorylcholine Copolymer: A Platform Strategy for Fabricating Antifouling Surfaces

Synthesis route of the doubly biomimetic copolymer PMNC

Messersmith, P. B, Macromolecular Bioscience, 2012, 12(7), 979–985

The polymer can be deposited onto a variety of substrates by dip-coating 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.

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Mussel-Inspired Adhesive Binders for High-Performance Silicon Nanoparticle Anodes in Lithium-Ion Batteries

Mussel-Inspired Adhesive Binders for High-Performance Silicon Nanoparticle Anodes in Lithium-Ion Batteries

Haeshin Lee, Adv. Mater. 2013, DOI: 10.1002/adma.201203981

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.

Synthesis of catechol-conjugated alginate and catechol-conjugated polyacrylic acid (Alg-C and PAA-C)

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Next planNext 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

47nm

2mg/ml BSA

原子力学显微镜

CaCO3

CAT-AlgDA

微囊

共聚焦显微镜

AlgDA 对 CAT的影响

190 200 210 220 230 240 250

-30

-20

-10

0

10

Elli

ptic

ity(m

deg)

Wavelength(nm)

Free CAT Alg

DA+CAT

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.

The ellipticity slightly increased and the negative peak at 222nm normally associated with classic α-helix structures was blue-shifted to 220.6 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.

Alginate Calcium TitaniumCatechol

O

ONH

O

O

O

O

2mm

NHO

HON

OH

OH

TOC

Alg DA

20min

EDTA

pH5.8

ED

TA

pH5.8

O OHO

OOC

COONaHO

OHO

HO

OHHO

O

HN

HN

HOHO

HN

TOC

软件

节能

环保

经济

创新

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