Biomedical Engineering Reference
In-Depth Information
Proteins can also be incorporated into PIC micelles by complexation with
block ionomers. Lysozyme, a positively charged enzyme, was encapsulated
into PIC micelles by complexation with negatively charged block copolymers
of PEG-b-PAsp and PAAm-b-PAA through electrostatic interaction in
aqueous medium.
31-33
The resultant PIC micelles were stable in mild
conditions but could be disintegrated by an enhanced salt concentration,
which provided an effective way to trigger the release of the incorporated
proteins.
34,35
Delivery of bioactive antibodies into the cytoplasm of living cells by PIC
micelles was achieved by Kataoka et al. for controlling cell growth
(Figure 9.18).
36
The charge density of a model protein, cytochrome c, was
temporarily increased by modification of the e-amines of lysine residues into
charge-conversional moieties, citraconic acid amide (Cit) or cis-aconitic acid
amide (Aco). As the positively charged lysines converted to the negatively
charged carboxylic groups by this modification, the modified proteins became
strongly anionic and the resulting charge density could be increased
significantly to form stable PIC micelles with cationic block copolymers even
at physiological salt concentrations. The charge-converted proteins and the
cationic block in the copolymer formed the core of the PIC micelle, and the
PEG block formed the surface shell. After the PIC micelles were internalized to
cells, the Cit and Aco rapidly degraded to reproduce the original lysines at the
endosomal pH of 5.5.
37,38
The charge-conversional intracellular antibody
delivery was expected to have high potential for the bioimaging of the
intracellular structures and functions of living cells, as well as for bio-
therapeutics to target intracellular antigens. Moreover, charge-conversional
PIC micelles could be used in intravenous protein delivery, based on the high
d
n
4
y
3
n
g
|
7
Figure 9.18
Preparation of the charge-conversional PIC micelles between IgG
derivatives and PEG-pAsp(DET) and the delivery of IgG into living
celles.
36
