Biomedical Engineering Reference
In-Depth Information
2.2.4
Cross-Linker-Mediated Chain Collapse
The use of a difunctional cross-linker to force the collapse of a
polymer chain is also a very efficient method to obtain SCPNs in a
controlled and straightforward manner.
Hawker's group has developed a synthetic approach using this
method, for the preparation of SCPNs under mild, room-temperature
conditions. They make use of isocyanate functionalised acrylic
polymers and a diamine cross-linker [42]. By varying the molecular
weight and mole percentage of isocyanates of the starting linear
copolymer, nanoparticles with diameters ranging from 8 to 20 nm
were obtained. Interestingly, the analysis of the collapse reaction
revealed that approximately 75% of the isocyanate groups along the
backbone underwent cross-linking, the other 25% being available
for further reactions with monofunctional amines, making them
ideal for bioconjugation.
Pomposo and co-workers used an aliphatic dialkyne cross-linker to
generate SCPNs from azide functionalised copolymers of diverse nature
[43, 44]. The method consisted of adding a solution of the cross-linker
very slowly to a solution of copolymer, by means of a syringe pump.
Similarly, Odriozola and co-workers prepared water soluble
SCPNs from azide functionalised acrylic copolymers and a dialkyne
cross-linker [45]. In that work, they introduced a gadolinium(III)
chelating unit (diethylenetriaminepentaacetic acid, DTPA) into the
cross-linker. This allowed the subsequent formation of Gd
3+
loaded
paramagnetic nanoparticles, which showed an increased relaxivity
over their mono-gadolinium counterparts, on a per gadolinium basis
(Scheme 2.4). This system represents the first example of potential MRI
contrast agents based on SCPNs with multiple gadolinium centres.
CO
2
H
i)
CO2H
DTPA
CuBr, 2 ,2´-bipy, DMF, r.t.
N3
CO
2
tBu
Gd3
+
(C l
-
)
3
N3
ButO2C
pH 6
N3
ii) TFA, CH2Cl2, 40 ºC
HO
2
C
CO
2
H
HO2C
CO2H
CO2tBu
H
N
N
H
N
N
N
=
O
O
O
O
Gd
O
O
O
O
N
O
N
O
O
O
N
N
N
N
O
H
H
Scheme 2.4
Formation of single-chain PNPs and loading with Gd III. Dashed
circles are used to highlight the newly formed 1,2,3-triazole rings during the
click cycloaddition. Reproduced from ref. [46] with permission.
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