fibrils is difficult due to the poor solubility of the peptides and the noncrystalline
nature of fibrils [58]. Thus, PEG-b-β-amyloid peptide block copolymers selfassembled into fibrils by assuming parallel β-strand conformation, providing structural information not only on the fibrillogenesis mechanisms, which are important
for the disease progression, but also on protein folding and self-assembly [56, 58].
Further supramolecular architectures of block copolymers also display unique
features for bridging polymer science and biology. Adi Eisenberg and colleagues
reported polymeric vesicles (i.e., polymersomes), which encapsulate bulk solution
phase in their hollow reservoir, constructed by controlling the length of the hydrophilic block and the hydrophobic block in poly(acrylic acid)-b-poly(styrene) copolymers [41, 59]. Polymersomes offer the possibility of incorporating hydrophilic
biomolecules in their hollow interior, which can be isolated from the external
environment, as well as hydrophobic molecules in the bilayer membrane. Similarly
to polymeric micelles, polymersomes can be formed from various intermolecular
forces, such as hydrophobic interactions with amphiphilic block copolymers [41,
59], electrostatic interactions from oppositely charged block copolymers [60], and
metal complexation [61]. Depending on the self-assembling type, the permeability
of the polymeric membrane of the polymersomes can be suitably tuned for regulating in–out diffusion of molecules and the molecular weight cut-off of the
membrane. Accordingly, polymersomes have been used for controlling the interaction and maintaining the activity of hydrophilic proteins in biological environments via their protection in the hollow core of polymersomes and the exchange of
small molecules through their membrane. Such is the case for polymersomes as
carriers of hemoglobin [62] or myoglobin [63] as well as enzyme-loaded
polymersomes [64] for creating nanoreactors. Worm-like micelles, reported by
Dennis Discher and colleagues [65], also present an elegant example on how the
shape of supramolecular constructs affect their interaction with the biological
environment. Thus, although the blood circulation of polymersomes was approximately 24 h, worm-like micelles remained in the bloodstream for more than 1 week
due to their high flexibility, which reduces macrophage uptake [65]. This high
versatility of block copolymer nanoassemblies for combining structural features
with bioactive functions has prompted their application in other areas of biotechnology, such as tissue engineering and regenerative medicine [66, 67], offering a
handy toolbox for developing therapeutic approaches with clinical translation.
Although the PEG surface of nanoassemblies minimizes their contact with
cellular membranes, their surface can be functionalized with ligands capable of
recognition of cell-specific surface receptors (such as antibodies, antibody fragments, aptamers, peptides, transferrin, and small molecules), which provides modulated cellular interaction and superior intracellular delivery [68]. Moreover,
ligand-installed assemblies have been used for enhancing the tumor targeting
because the targeted receptors are displayed in cancer cells or tumor-associated
cells more frequently than in healthy tissues [68]. In addition, due to the presence of
multiple ligand molecules on the surface of nanoassemblies, the binding affinity of
the whole system can be enhanced by multivalent binding, which augments their
internalization rate [69]. Ligand-installed nanoassemblies can also be used for
Bridging Polymer Science and Medicine Through Supramolecular Nanoassemblies
257
nature of fibrils [58]. Thus, PEG-b-β-amyloid peptide block copolymers selfassembled into fibrils by assuming parallel β-strand conformation, providing structural information not only on the fibrillogenesis mechanisms, which are important
for the disease progression, but also on protein folding and self-assembly [56, 58].
Further supramolecular architectures of block copolymers also display unique
features for bridging polymer science and biology. Adi Eisenberg and colleagues
reported polymeric vesicles (i.e., polymersomes), which encapsulate bulk solution
phase in their hollow reservoir, constructed by controlling the length of the hydrophilic block and the hydrophobic block in poly(acrylic acid)-b-poly(styrene) copolymers [41, 59]. Polymersomes offer the possibility of incorporating hydrophilic
biomolecules in their hollow interior, which can be isolated from the external
environment, as well as hydrophobic molecules in the bilayer membrane. Similarly
to polymeric micelles, polymersomes can be formed from various intermolecular
forces, such as hydrophobic interactions with amphiphilic block copolymers [41,
59], electrostatic interactions from oppositely charged block copolymers [60], and
metal complexation [61]. Depending on the self-assembling type, the permeability
of the polymeric membrane of the polymersomes can be suitably tuned for regulating in–out diffusion of molecules and the molecular weight cut-off of the
membrane. Accordingly, polymersomes have been used for controlling the interaction and maintaining the activity of hydrophilic proteins in biological environments via their protection in the hollow core of polymersomes and the exchange of
small molecules through their membrane. Such is the case for polymersomes as
carriers of hemoglobin [62] or myoglobin [63] as well as enzyme-loaded
polymersomes [64] for creating nanoreactors. Worm-like micelles, reported by
Dennis Discher and colleagues [65], also present an elegant example on how the
shape of supramolecular constructs affect their interaction with the biological
environment. Thus, although the blood circulation of polymersomes was approximately 24 h, worm-like micelles remained in the bloodstream for more than 1 week
due to their high flexibility, which reduces macrophage uptake [65]. This high
versatility of block copolymer nanoassemblies for combining structural features
with bioactive functions has prompted their application in other areas of biotechnology, such as tissue engineering and regenerative medicine [66, 67], offering a
handy toolbox for developing therapeutic approaches with clinical translation.
Although the PEG surface of nanoassemblies minimizes their contact with
cellular membranes, their surface can be functionalized with ligands capable of
recognition of cell-specific surface receptors (such as antibodies, antibody fragments, aptamers, peptides, transferrin, and small molecules), which provides modulated cellular interaction and superior intracellular delivery [68]. Moreover,
ligand-installed assemblies have been used for enhancing the tumor targeting
because the targeted receptors are displayed in cancer cells or tumor-associated
cells more frequently than in healthy tissues [68]. In addition, due to the presence of
multiple ligand molecules on the surface of nanoassemblies, the binding affinity of
the whole system can be enhanced by multivalent binding, which augments their
internalization rate [69]. Ligand-installed nanoassemblies can also be used for
Bridging Polymer Science and Medicine Through Supramolecular Nanoassemblies
257