Synthesis of novel bis-triazolinedione crosslinked amphiphilic polypept(o)ide nanostructures

Owing to their wide range of inherent functionality, hydrolytic stability, biodegradability, and low toxicity, polypeptide-based materials have been increasingly exploited for controlled drug release applications. More recently, the incorporation of poly(α-peptoid)s such as poly(sarcosine) into polypeptide-based materials has been investigated owing to their potential as naturally derived “stealth polymers.” Here the synthesis of novel amphiphilic polypept(o)ide nanoparticles is described utilizing silica templates as a macroinitiator for the ring-opening copolymerization of l-tryptophan and d/l-phenylalanine NCAs and subsequent chain extension with sarcosine NCA. These particles are subsequently crosslinked utilizing the TAD-indole “click” chemistry and the silica templates are eroded via treatment with HF yielding core crosslinked amphiphilic polypept(o)ide nanostructures. This synthetic strategy offers a unique platform to yield naturally-derived degradable core-crosslinked nanostructures, which may have the potential to be utilized in the future as delivery vehicles for hydrophobic small molecules.