Li Bowen, Bao Jianwei, Huang Yan, Liu Jikang, Yan Xuehai, Zou Qianli
School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
Small. 2025 Apr;21(15):e2409038. doi: 10.1002/smll.202409038. Epub 2024 Nov 21.
The integration of integrin-binding peptides within self-assembling building blocks is crucial for the development of targeted nanoarchitectonics. However, such constructs typically incorporate only a single integrin-binding peptide, limiting their multifunctionality. Herein, a rationally designed self-assembling peptide with dual integrin-binding motifs for α5β1 and αvβ3 is presented. This peptide forms highly ordered nanofibers or nanoparticles (VH-NPs) with tailored secondary structures. In vitro and in vivo studies demonstrate that VH-NPs target activated hepatic stellate cells via dual-integrin interactions, enabling selective targeting to fibrotic livers and suppressing α5β1 and αvβ3. Notably, VH-NPs can encapsulate rhein through noncovalent interactions, resulting in peptide-rhein nanoarchitectonics that display augmented antifibrotic effects. These findings highlight the potential of self-assembling peptides that leverage multiple targets and therapeutic modules as a promising strategy for constructing multifunctional nanoarchitectonics.
整合素结合肽在自组装结构单元中的整合对于靶向纳米建筑学的发展至关重要。然而，此类构建体通常仅包含单一的整合素结合肽，限制了它们的多功能性。在此，我们展示了一种合理设计的具有针对α5β1和αvβ3的双整合素结合基序的自组装肽。这种肽形成具有定制二级结构的高度有序的纳米纤维或纳米颗粒（VH-NPs）。体外和体内研究表明，VH-NPs通过双整合素相互作用靶向活化的肝星状细胞，能够选择性地靶向纤维化肝脏并抑制α5β1和αvβ3。值得注意的是，VH-NPs可以通过非共价相互作用封装大黄酸，从而产生具有增强抗纤维化作用的肽-大黄酸纳米建筑学。这些发现突出了利用多个靶点和治疗模块的自组装肽作为构建多功能纳米建筑学的有前景策略的潜力。
