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1. Introduction
DNA–copolymers composed of either water-soluble or hydro-
phobic polymer segments of various compositions are
nowadays available through both organic and molecular bio-
technology routes.
[1]
Amphiphilic DNA–polymer can self-
assemble in aqueous solution into micelles of various shapes
such as spherical core–shell micelles
[1a,b]
or vesicles,
[1c]
which
are closed spherical copolymer shells. Sizes in the sub-microm-
eter range could be achieved by this mechanism of microphase
separation.
[1]
Of particular interest is Watson–Crick base pairing
between complementary nucleotide sequences, which assemble
to form a double helix through hybridization to enable further
either structure manipulations such as stimulation of mor-
phological transitions from spherical to rod-like micelles,
[1a,b]
immobilization of self-assembled struc-
tures on surfaces
[2]
as well as chemical
functionalization using a labeled comple-
mentary sequence to target cell surface
receptors for instance.
[1a,b]
Besides hybridization, nucleotide
sequences might however interact spe-
cifically with a target moiety. We ourselves
observed a positive response of bacteria
to surface-tethered nucleotide sequences
and self-assembled structures thereof.
[2]
Although no specificity of the nucleo-
tide sequences towards Escherichia Coli
could be expected, the bacteria produced
curli, which are organelles of adhesion
expressed upon interaction with surfaces
coated with nucleotide sequences.
[2a]
Aptamers however are synthetic single
stranded nucleotide sequences that
undergo remarkable molecular recogni-
tion properties.
[3]
Binding affinities are
comparable to those achieved with antibodies due to an effi-
cient in vitro combinatorial strategy of selection called system-
atic evolution of ligands by exponential enrichment (SELEX),
a major advantage over production of antibodies.
[3a]
The spe-
cific and complex 3D shape of aptamers, which are short
single-stranded nucleotide sequences (ssDNA or RNA) ena-
bles binding with high specificity to a wide variety of targets
from single molecules to complex mixtures or whole organ-
isms. We therefore describe herein the grafting of the aptamer
against the immunoglobulin E (IgE), an allergy biomarker, to
a hydrophobic polymer segment. Anti-IgE aptamers have been
shown to block interactions with the IgE receptor with high
affinity to inhibit IgE-mediated serotonin release from cells in
tissue culture.
[3a]
Anti IgE-apatmers might therefore prove to be
useful for blocking local inflammatory responses mediated by
IgE. With future biomedical applications in mind and the pos-
sibility to use methods developed in polymer science to investi-
gate the system under consideration, we thus report in here the
grafting of the IgE-aptamer to a poly(2-alkyl-2-oxazoline) with
N-Boc protected amino acid and alkenyl side chains. This syn-
thetic macromolecule is a bioinspired amphiphilic copolymer
with a structural relation to polypeptides, which therefore
reveals high potential for biomedical applications.
[4]
The emul-
sification methodology to prepare both aqueous and liquid oil
cores enables the facile encapsulation of various water soluble
or hydrophobic active agents with efficient applicability in var-
ious fields like pharmacy, food and cosmetics.
[5]
Of particular
interest is the combination of the emulsification process with
Polymer–Aptamer Hybrid Emulsion Templating Yields
Bioresponsive Nanocapsules
Dawid Kedracki, Plinio Maroni, Helmut Schlaad, and Corinne Vebert-Nardin
*
This article describes the synthesis of a DNA–polymer, being the nucleotide
sequence an aptamer selected in vitro to target specifically the immuno-
globulin E (IgE) protein, an allergy biomarker. Subsequent to coupling to
poly(2-alkyl-2-oxazoline) with N-Boc protected amino acid side chains, the
resulting amphiphilic DNA–polymer hybrid composed of the water-soluble
DNA fragment grafted to the hydrophobic polymer segment can be regarded
as a high molecular weight analogue of a surfactant. It is demonstrated that
the copolymer–aptamer stabilizes efficiently submicrometer size oil-in-water
and water-in-oil emulsions, by dynamic light scattering, microscopy, and
reflectometry. Particularly interesting is that the aptamer remains functional
after coupling to a polymer backbone, stabilization of the emulsion droplets,
and locking of the structure subsequent to cross-linking polymerization. The
resulting nanocapsules still target specifically the IgE protein. The biological-
stimulus responsiveness of the structures is of high potential for future
developments of carriers for sustained and targeted delivery.
DOI: 10.1002/adfm.201302475
MSc D. Kedracki, Dr. P. Maroni, Prof. C. Vebert-Nardin
University of Geneva
Faculty of Sciences
Department of Inorganic and Analytical Chemistry
Quai Ernest Ansermet 30, 1211, Geneva 4, Switzerland
E-mail: corinne.vebert@unige.ch
Dr. H. Schlaad
Max Planck Institute of Colloids and Interfaces
Department of Colloid Chemistry
Research Campus Golm,
14424, Potsdam, Germany
Adv. Funct. Mater. 2014, 24, 1133–1139