Aqueous Ring-Opening Polymerization-Induced Self-Assembly (ROPISA): Tailoring Anisotropic Nanoparticles through Amino Acid N-Carboxyanhydride (NCA) Monomer Selection

The synthesis of anisotropic nanoparticles by polymerization-induced self-assembly (PISA) remains challenging yet holds significant potential for biomedical applications. In this context, aqueous ring-opening polymerization-induced self-assembly (ROPISA) of N-carboxyanhydrides (NCAs) has emerged as a promising strategy, offering a straightforward route to peptide-based nanomaterials. The present study was undertaken to evaluate the versatility of aqueous ROPISA across a range of NCAs, elucidating how their hydrophobicity and the chemical structure of the lateral chains provide access to nanoparticle anisotropy. A comparative analysis was conducted between NCAs with different protecting groups and those derived from distinct hydrophobic amino acids. Beyond hydrophobicity, the aqueous ROPISA of glycine NCA, phenylalanine NCA, and tyrosine NCA revealed the crucial role of additional factors such as the hydrophilic/hydrophobic balance, π-π stacking interactions, and hydrogen bonding in shaping nanoparticle anisotropy. Overall, this work highlights the broad applicability of aqueous ROPISA across a wide range of NCA monomers and its ability to generate tailored worm-like nanoparticles for advanced applications.