Xiaoxiong Jin,Wanying Wang,Hui Liu,Jing Zhao,Pengfei Li,Aoting Li,Ziyuan Song
Poly(l-glutamic acid)s (PLGs) are promising bone-targeting ligands due to their high molecular weight and facile preparation. Nevertheless, the bone-targeting efficiency of PLGs is still relatively low, validating the necessity to further enhance targeting through structural optimization. Herein, we report the use of a heteropolypeptide strategy to improve the bone targeting of PLGs through the incorporation of another side-chain functionality for enhanced affinity with bone tissues. Specifically, the introduction of cationic amino or aromatic phenolic side-chain residues resulted in a ∼2.3-fold or ∼1.6-fold increase in the in vivo bone targeting, respectively. Cationic modification not only improved the affinity with bone minerals but also exhibited prolonged retention in the bone tissues for more than 60 days. This work highlights the use of a heteropolypeptide library to screen and optimize the performance of polypeptide materials, offering promising bone-targeting polymeric materials for the design of bone-related nanomedicine.
Heteropolypeptides bearing two or more functional side chains are promising polymeric materials for various biomedical applications. However, conventional preparation of heteropolypeptides relies on the synthesis and purification of each N-carboxyanhydride (NCA) monomer in a separate manner, which substantially increases the time and cost. Herein, we report the facile preparation of heteropolypeptides with up to 86% yield within several hours, which are obtained from a mixture of crude NCA monomers. The combination of n-hexane precipitation and biphasic segregation effectively removed >90% impurities from crude NCA mixtures, allowing for the successful polymerization process. Various heteropolypeptides with monomodal distribution and narrow dispersity were efficiently prepared, whose compositions were predetermined by the feeding ratios of amino acids. We believe that this work significantly simplifies the preparation of various heteropolypeptides, boosting the downstream studies of these promising materials.
危险品化学品经营许可证（带存储）