Thanks to their high biocompatibility, polypeptides are promising polymers for designing biomaterials to be used in medicine for various applications (tissue engineering, drug delivery, etc.). Generally, polypeptides are synthesized via ring opening polymerization (ROP) of N-carboxyanhydride (NCA) in anhydrous organic solvents. While NCA are known to degrade in presence of water, we recently reported an unprecedented ROP of NCA in aqueous buffered solution using an amino-terminated poly(ethylene glycol) (PEG) macroinitiator. Our first observations indicate that this macroinitiator could protect NCA monomers from hydrolysis through spontaneous in situ self-assembly (ISA). We have called this process ROPISA, a methodology that one can set-up 1) to avoid the use of toxic solvent and 2) to create nanoparticles from NCA in 1 step without the need of further purification or nanoprecipitation steps. Herein, we present a comprehensive study of the ROPISA process with PEG5 kDa-NH2 macroinitiator and either g-benzyl-L-glutamate NCA (BLG-NCA) or L-leucine NCA (Leu-NCA) monomers. ROPISA was used to prepare amphiphilic block copolymers with different molar masses, and concomitantly nanostructures in pure aqueous media. With other polymers, the nanostructure obtained upon PISA are related to the volume fraction of the hydrophilic and of the hydrophobic blocks. In contrast, our ROPISA process was controlled by the secondary structure of the polypeptides, a conformational feature that stabilized unusual anisotropic rod-like structures. We found that the chemical nature of the NCA monomer and the secondary structure of the polypeptide both define the dimension parameters of the elongated nanostructures. β-sheet forming polypeptides made of L-leucine strongly favored the formation of longer rods with high aspect ratio, as compared to α-helical polypeptides made of BLG units. These results showed that ROPISA allows the preparation of nanomaterials with tunable anisotropy.

Aqueous ROPISA of N-carboxyanhydrides: controlling anisotropy through the secondary structure of polypeptide

ACS Spring 2022

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