Single-Chain Polymer Nanoparticles for Application in Nanomedicine - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 29

2.2.3 Hetero-Bifunctional Chain Collapse

Another strategy to synthesise SCPNs consists of decorating the
polymer backbone with two diff erent self-complementary motifs.
Loinaz and co-workers have developed a strategy to produce
poly(methyl methacrylate) SCPNs [36] at room-temperature by
means of an intramolecular CuI-catalysed [3+2] cycloaddition,
or “click” reaction, between azide and alkyne functional groups
present in the same polymer backbone. Click chemistry [37, 38],
and specifically the CuI-catalyzed [3+2] cycloaddition of alkynes
and azides [39-41], is a selective and very efficient kind of reaction
that can be performed under extremely mild conditions with high
yields, good functional group tolerance and negligible by-products.
The very mild conditions required for the chain-collapse makes this
method ideal for the fabrication of SCPNs with polymers that are not
stable at high temperatures.
In addition, the authors demonstrated the possibility of
functionalising the resulting nanoparticles very easily with suitable
biomolecules. To achieve that, an excess of azide groups was added
to the polymer backbone. After the formation of the nanoparticle, an
alkyne-containing molecule (propargylglycine) was attached to the
surface by means of a second click reaction (Scheme 2.3).

Scheme 2.3 Chain-collapse through intramolecular click cycloaddition and
further functionalisation with a suitable biomolecule by means of a second
click cycloaddition. Reproduced from ref. [36] with permission.

However, one of the major drawbacks of this method is the
difficulty in the synthesis of the precursor copolymers, which need to
have the two complementary reactive groups randomly distributed
over the chain. This problem is solved by the use of a suitable
difunctional cross-linker, as we will see in the following section.