Nanomedicine and nanotechnology emerged to address unmet medical needs in cancer and other diseases aiming to improve quality-of-life. The use of well-defined biodegradable polypeptides increases the safety of the nanostructures employed, which will be degraded and excreted safely from the body. However, the self-assembly of amphiphilic block copolymers into defined nanoparticles (NPs) is limited to dilute copolymer solutions (&lt;1%), representing a significant disadvantage for commercial applications due to obvious problems in manufacture and scaling-up processes. A solution to this problematic is the so-called polymerization-induced block copolymer self- assembly (PISA). PISA is well established in the bulk for toughened thermosets and elastomers formed by step polymerization. Nevertheless, it has never been applied to the synthesis of polypeptide-based NPs made by ring opening polymerization. We describe for the first time, the ring-opening of N-Carboxyanhydrides (NCA) Polymerization Induced Self-Assembly (NISA) of block copolymer nanoparticles via non-aqueous dispersion polymerization. Additionally, the amino acid methionine was employed as a redox-responsive hydrophobic block. The supramolecular organization of those structures during NISA provided an array of nanoparticles (i.e. micelles, worms and vesicles) depending on the hydrophobic block length as well as the solid contents and a phase diagram could be constructed. Those NPs demonstrated to be redox-sensitive and disassemble when using H2O2 as model ROS species. The Redox behavior of methionine-based vesicles was additionally observed “in situ” by using liquid TEM techniques. Moreover, the versatility of this strategy allowed to introduce orthogonal functionalities at the NPs surface by simply using a certain proportion of bifunctional initiators. Those functionalities can ultimately be used for bioconjugation of dyes, peptides, drugs, or antibodies. NISA allow us to produce NPs in high copolymer concentrations which can be easily manufactured aiming for industrial translation. Due to the versatility of the method, this biodegradable and biocompatible NPs can be used in many biological applications (i.e. as carriers for drug/peptide/protein delivery or imaging agents).

Stimuli-responsive polypeptide-based nanoconstructs

2019 Fall National Meeting

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