Single-Chain Polymer Nanoparticles for Application in Nanomedicine - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 27

continuous addition of the linear polymer to the reaction mixture. If
the cross-linking reaction rate is faster than the addition rate, then
the concentration of the reactive open-chain species will always be
ultra-low, while the concentration of the unreactive nanoparticles will
be constantly growing. Under these conditions, no intermolecular
cross-linking reactions, leading to gelation or coupling of individual
nanoparticles, are observed. To achieve this, Hawker chose the
thermal-induced coupling of benzocyclobutene (BCB) units at 250 ° C.
A series of BCB copolymers with styrene, methyl methacrylate, or
n -butyl acrylate were used for this study.
Later on, Harth and co-workers reported the vinylbenzosulfone
cross-linking monomer, which can be used as an alternative to
BCB, and has the advantage of being easier to synthesise [30]. They
copolymerized this precursor with styrene or benzyl acrylate. In the
latter case, the subsequent deprotection of the benzyl ester groups
resulted in the formation of SCPNs that were soluble in physiological
conditions, and could therefore be envisaged as promising candidates
for biomedical applications. In a subsequent work, the authors
brilliantly demonstrated the usefulness of these nanoparticles as
efficient nanocarriers for the intracellular delivery of peptide-based
therapeutics [31].
Vinylbenzosulfone units were also used for the fabrication of
SCPNs with single conducting polymers embedded in polystyrene,
which resulted in a considerable increase in quantum efficiency [32].
Olefin cross-metathesis has also been used to induce the
intramolecular cross-linking of polycarbonates with pending vinyl
groups, as reported by Coates and co-workers [33]. The cross-
linking was eff ected by the addition of a ruthenium catalyst into a
dilute polymer solution. In this work, the formation of molecular
nanoparticles was confirmed by atomic force microscopy (AFM)
through visualisation of individual molecules at diff erent stages of
the cross-linking.
So far we have seen the fabrication of SCPNs by means of covalent
cross-links between suitable pending groups of a polymer-chain.
However, the collapse of polymer chains can also be accomplished
through non-covalent interactions, such as hydrogen bonds, which
leads to supramolecular single-chain nanoparticles. This is especially
interesting from a biological point of view, due to the analogy with
the folding of biomacromolecules. While synthetic copolymers are by
no means as structurally complex as natural polymers, the continued