Controlled Synthesis and Biomedical Applications of Cystine-based Polypeptide Nanomaterials

Polypeptides are a kind of polymers with amino acids and their derivatives as structural units. Given their excellent properties, such as various structural units, excellent biosafety, facile modification, sensitive bioresponsiveness, and unique secondary structures, polypeptides have superior advantages for biomedical applications. Cystine is a dimer of cysteine linked by a disulfide bond, which can be synthesized into a bifunctional cysteine N-carboxylanhydride (Cys(2) NCA) monomer by cyclization reaction. Through the ring-opening polymerization of Cys(2) NCA and another monofunctional amino acid NCAs, a series of disulfide-crosslinked polypeptide nanomaterials could be controllably synthesized with diverse chemical structures, adjustable particle sizes, excellent stability, and biological responsiveness to achieve the controlled delivery of imaging agents and bioactive molecules. Based on the recent studies of our group, this review summarized the research progress of single-component, double-component, and multi-component cystine-based polypeptide nanomaterials. To be specific, the functions of single-component cystine-based polypeptide nanomaterials are limited. The double-component polypeptide nanomaterials, which are developed on the basis of single-component ones, show improved drug loading rates, expanded types of loading drugs, and a more stable nanostructures. In order to achieve a more exclusive function as a drug delivery platform, we expect to use the synergy and cascade action of different functionalized amino acids to produce multi-component polypeptide nanomaterials. The multicomponent nanoplatform might provide reliable solutions for precision medicine. At last, their opportunities and challenges in clinical application and the new medical application fields were predicted.