Structural Analysis of Unimer Nanoparticles Composed of Hydrophobized Poly(amino acid)s

Abstract

Amphiphilic random copolymers of poly(γ-glutamic acid)-graf t-L-phenylalanine (γ-PGA-Phe), with various lengths of γ-PGA main chains (molecular weight of 70, 140, and 220 kDa) plus hydrophobic moieties of Phe groups (grafting degree 12−60%), self-assembled in aqueous media to form nanoparticles (NPs). The aggregation number (N agg ) could be adjusted according to their molecular structures as well as the preparative methods/conditions. The γ-PGA-Phe NPs were further characterized by means of dynamic and static light scattering, small-angle neutron scattering, as well as steady-state fluorescence measurements/quenching techniques. The single chain state had hydrophobic domains, and formed spherical structures, herein called unimer NPs, and were obtained using molecular weights of γ-PGA higher than 140 kDa conjugated with Phe at 27−42% due to the balance of hydrophobicity/hydrophilicity along the single polymer chain. The number of hydrophobic domains in one NP (N domain ), estimated by means of fluorescence quenching techniques and the rigidity of the inner particles detected by dipyrene fluorescence demonstrated that the N domain and the rigidity were affected by the particle size and preparative methods. In addition, the effect of pH on the stability of the unimer NPs indicated a reduction of the N domain upon the pH, supporting a loose packing due to hydrophobic association under alkaline conditions.

Advances in single chain technology

“…Hence, Akashi and coworkers 91,92 reported unimer nanoparticles composed of hydrophobized poly(amino acid)s based on amphiphilic random copolymers of poly(g-glutamic acid)-graft-L-phenylalanine (g-PGA-Phe) selfassembled in aqueous media. Hence, Akashi and coworkers 91,92 reported unimer nanoparticles composed of hydrophobized poly(amino acid)s based on amphiphilic random copolymers of poly(g-glutamic acid)-graft-L-phenylalanine (g-PGA-Phe) selfassembled in aqueous media.…”

Simulation guided design of globular single-chain nanoparticles by tuning the solvent quality

“…The control of the primary structure of synthetic polymers has indeed received significant attention in recent years, as pioneered by Lutz et al 23 , and it is envisioned that, working along this line, the control over the secondary and tertiary structure of synthetic polymers will be achieved via singlechain technologies 24 . At the present time two examples of non-covalent bonded SCNPs, constructed by tuning the hydrophilic/hydrophobic sequence and interactions of a random copolymer, have been recently reported 25,26 . In such reported cases the single-chain self-folding is reversible, i.e., the globular conformations are lost when restoring good solvent quality for all monomers.…”

Multi-orthogonal folding of single polymer chains into soft nanoparticles

“…The controlled folding of single polymer chains into soft nanoparticles has attracted significant interest due to its (partial) resemblance to the polypeptide chain collapse process into the compact native state 4 . In recent years, several intrachain cross-linking chemistries have been introduced for single-chain nanoparticle (SCNP) synthesis involving covalent , noncovalent [29][30][31][32][33][34][35] and dynamic covalent bonds [36][37][38][39] , most of them comprising a single cross-linking type. In addition, techniques like intrachain homocoupling, intrachain heterocoupling or cross-linking induced collapse are currently available to promote the intramolecular folding of individual polymer chains to SCNPs 40 .…”