School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
Small. 2023 Nov;19(45):e2304675. doi: 10.1002/smll.202304675. Epub 2023 Jul 11.
Therapeutic peptides have attracted increasing attention as anti-fibrotic drug candidates. However, the rapid degradation and insufficient liver accumulation of therapeutic peptides have seriously hampered their clinical translation. Here, the use of supramolecular nanoarchitectonics is reported to fabricate nanodrugs from therapeutic peptides for treating liver fibrosis. Self-assembling antagonist peptides are rationally designed and manipulated into uniform peptide nanoparticles with well-defined nanostructures and uniform sizes. Significantly, the peptide nanoparticles show enhanced accumulation in liver sites and limited distribution in other tissues. In vivo results show that the peptide nanoparticles exhibit greatly enhanced anti-fibrotic activity compared to the pristine antagonist along with good biocompatibility. These results indicate that self-assembly is a promising nanoarchitectonics approach to enhance the anti-fibrotic activity of therapeutic peptides for treating liver fibrosis.
治疗性肽作为抗纤维化药物候选物引起了越来越多的关注。然而，治疗性肽的快速降解和肝内蓄积不足严重阻碍了其临床转化。在这里，报告了利用超分子纳米结构来制备治疗性肽的纳米药物，以治疗肝纤维化。合理设计了自组装的拮抗剂肽，并将其操纵成具有明确纳米结构和均匀尺寸的均匀肽纳米颗粒。重要的是，肽纳米颗粒在肝部位的蓄积增强，而在其他组织中的分布受限。体内结果表明，与原拮抗剂相比，肽纳米颗粒表现出大大增强的抗纤维化活性，同时具有良好的生物相容性。这些结果表明，自组装是一种很有前途的纳米结构方法，可以增强治疗性肽的抗纤维化活性，用于治疗肝纤维化。
