Abstract：
Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.
摘要：
多肽材料提供可扩展性，生物相容性，和生物降解性，使它们成为生物医学应用的理想平台。然而,制备具有特定官能团的多肽，如氨基脲部分，仍然具有挑战性。这项工作报告，第一次,包含氨基脲部分的明确定义的甲氧基封端的聚（乙二醇）-b-多肽杂化嵌段共聚物（HBCPs）的直接合成。该合成涉及实施环境稳定的N-苯氧羰基官能化α-氨基酸（NPCA）前体的直接聚合，从而避免处理不稳定的N-羧基酸酐(NCA)单体。所得的含有氨基脲部分的HBCP能够容易地与醛/酮衍生物官能化，形成pH可裂解的氨基脲键，用于定制的药物释放。特别是,细胞内pH触发的氨基脲部分水解恢复了最初的氨基脲残基，促进内溶酶体逃逸，从而改善治疗结果。此外，将低氧探针（Ir（btpna）（bpy）2）整合到pH响应性纳米药物中，可以对酸性和低氧肿瘤微环境产生连续反应，能够精确检测转移性肿瘤。设计定制功能多肽的创新方法有望用于高级药物递送和精确疗法。本文受版权保护。保留所有权利。
