Biomedical Engineering Reference
In-Depth Information
the polymer chains causes steric repulsion to resist protein adsorption due to
an unfavorable decrease in entropy.
11,12
On the other hand, a long-chain
polymer-coated surface might eventually cause protein adsorption after their
reconfiguration if the protein could be weakly adsorbed on a long-chain
polymer. All these factors will decide the final resistance of the surfaces. In
other words, the surface resistance is conditional even if ideal protein-resistant
polymers (such as PEG) are used.
Zwitterionic materials all share the same characteristic in a homogenous 1:1
positive to negative charge distribution on a nanometer scale, which also could
be used as a simple design rule for new zwitterionic materials to resist protein
nonspecific adsorption through mimicking the homogenous charge distribution
feature. Following this design rule, peptides with alternative charge distributions
by natural amino acids (Glu
2
, Asp
2
, and Lys
+
) have been synthesized and
proved to be highly resistant to nonspecific protein adsorption. Also, poly-
methacrylates with the same charge feature also show excellent resistance. In
fact, the positive charge could be contributed by primary to quaternary amines
as well as other monovalent positively charged groups, while the negative charge
could be given by 2SO
3
2
, 2COO
2
, monoesters of phosphates, and also other
possible monovalent negatively charged groups. Thus, the new zwitterionic
polymers
d
n
4
y
3
n
g
|
7
with
homogenous
charge
distribution
could
cover
a
very
wide
spectrum of materials.
Moreover, the multiple choice for positive and negative charge providers in
zwitterionic polymers facilitates their versatility for conjugation and functiona-
lization, which is essential for drug delivery systems. For example, the CB
polymer provides such a solution.
18
Researchers always face a compromise
between maximizing the numbers of functional groups for immobilization of
bio-recognition molecules and maintaining resistance to nonspecific adsorption.
Conventionally, PEGs with reactive end groups, such as COOH and NH
2
, are
always partially mixed in PEG-based coatings for chemical immobilization of
bio-recognition molecules. The unreacted end groups after immobilization
become surface defects for nonspecific protein adsorption.
18
However, pCBMA
could play dual roles in preventing nonspecific protein adsorption and
conjugating with amine groups on bioactive molecules by the large number of
carboxyl groups on pCBMA. Furthermore, the conjugation through 1-ethyl-3-
(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide (EDC/NHS)
chemistry will not degrade the resistance to nonspecific protein adsorption since
the remaining ester groups of NHS are hydrolyzed to carboxylate anions, which
are paired with cationic quaternary amines to form zwitterionic structures to
resist nonspecific protein adsorption. Such an advantage is demonstrated by
high reproducibility and sensitivity in undiluted serum of both surface plasmon
resonance (SPR) biosensors
19
and superparamagnetic nanosphere-based
immunoassay.
30
Thus, this makes poly(carboxybetaine) (PCB), represented by
pCBMA, a universal polymer for ''theranostics''.
Besides a unique capability in conjugation, the zwitterionic related molecules
can also provide more choices through the format change response to the
