Facile preparation, structural modulation, and bone-targeting of single-chain polypeptide nanoparticles

The bioapplication of single-chain polymer nanoparticles (SCNPs) is limited by the use of non-degradable polymer precursors and harsh intrachain crosslinking conditions. Herein, we report the facile preparation of single-chain polypeptide nanoparticles in an aqueous environment through aza-Michael addition. The size, compactness, and stimuli-responsiveness were easily modulated, offering a library of polypeptide nanoparticles for biomedical studies. The application was demonstrated through surface modification, yielding anionic, bone-targeting nanoparticles. We believe that this work highlights the use of polypeptides and mild crosslinking conditions for SCNP preparation, offering a series of well-defined nanoparticles for further property and application studies.