Download Amino Acid – Based Zwitterionic Antifouling Polymers: Development

Amino Acid – Based Zwitterionic Antifouling Polymers: Development,
Biofouling Properties and Applications
Wenchen Li, Qingsheng Liu, Lingyun Liu*.
Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325.
Statement of Purpose: Surfaces with antifouling
properties are critical to many applications, such as
biomedical implants, biosensors, drug delivery, and ship
hulls. Due to unique zwitterionic and biomimetic nature
of amino acids, we developed a group of amino acidbased zwitterionic (AAZ) antifouling monomers, derived
from natural amino acids – serine (Ser), ornithine (Orn),
lysine (Lys), aspartic acid (Asp), and glutamic acid (Glu),
respectively. The structures of five amino acid-based
zwitterionic monomers together with their precursors are
summarized in Fig. 1. The antifouling properties of the
surface-grafted pAAZ to resist protein adsorption, cell
adhesion, and long-term bacterial attachment were
explored. The cytotoxicity of monomers and nanogels
Figure 1. Structures of five amino acid-based zwitterionic
made from pAAZ were also investigated.
(AAZ) antifouling monomers. The amino acid portion in the
vinyl monomers is shaded.
Methods: The SerMA, OrnAA, and LysAA were
synthesized by reacting the terminal group of the side
chain of the corresponding amino acid (-OH or -NH2)
with methacryloyl chloride. To obtain AspAA and
GluAA, aspartic aid and glutamic acid, with both -amine
and -carboxylic acid protected, were first coupled with a
vinyl monomer; the intermediate product was then treated
with trifluoroacetic acid to remove the protected groups to
generate the zwitterionic structure. The corresponding
polymer brushes were then prepared on gold via the
Figure 2. Adsorption from 100% human blood serum and
surface-initiated photoiniferter-mediated polymerization.
plasma onto the bare and pAAZ-modified surfaces.
The nonspecific adsorption from undiluted human blood
serum and plasma was studied by surface plasmon
resonance (SPR). Cell adhesion on pAAZ grafted surfaces
was evaluated against bovine aortic endothelial cells. P.
aeruginosa (Gram-negative) and S. epidermidis (Grampositive), as two model bacterial species, were used to
Figure 3. Attachment of P. aeruginosa (a and b) and S.
evaluate biofilm formation (14 days) on the pAAZEpidermidis (c and d) after 14-day culture. Bar = 10 μm.
grafted surfaces. Considering multiple potential
The bacterial accumulation on the pAAZ surfaces after 9
applications (e.g. medical devices and drug delivery) of
or 14 days was even lower than on the surfaces grafted
the antifouling materials, we further systematically
with poly[poly(ethyl glycol) methyl ether methacrylate,
evaluated the cytotoxicity of both monomers and polymer
one of the most common antifouling materials known to
nanogels made from AAZ at various concentrations.
date. Very low cytotoxicity was observed for all tested
Results: We developed a group of amino acid-based
amino acid-based monomers and polymer nanogels using
zwitterionic polymers which are ultralow fouling,
cytotoxicity assay.
biomimetic, and possess multiple reactive groups for
Conclusions: The pAAZ-grafted surfaces effectively
further conjugation. These materials are highly resistant to
resist protein adsorption from undiluted human blood
serum/plasma adsorption, cell attachment, and long-term
serum and plasma. Moreover, the polymers can highly
bacterial adhesion. All five polymers can significantly
resist adhesion from endothelial cells, and prevent long
reduce protein adsorption by more than 90% compared to
term biofilm formation from P. aeruginosa and S.
the bare gold surface (Fig. 2). The adsorption variance
epidermidis. Not only such materials can be coated on the
among 5 polymers are related to their structural
biomedical device surfaces to prevent biofouling, they can
differences. No cell attachment was observed on pAAZalso be utilized to create or coat nanoparticles (e.g.,
grafted surfaces. The biofilm formation assay
nanogels, gold nanoparticles) for a variety of applications
demonstrates that compared to the unmodified gold, the
such as targeted drug delivery for cancer treatment.
pAAZ surfaces were highly resistant to bacterial adhesion
References:
after culturing for 1, 5, 9, or even 14 days, representing at
Liu QS. Acta Biomaterialia. 2014; 10: 2956-2964.
least 95% reduction at all time points compared to the
Li WC. Langmuir. 2014; 30: 12619-12626.
control unmodified surfaces (Fig. 3).
Liu QS. Langmuir. 2016; 32: 7866-7874.