Cixi Institute of Biomedical Engineering，Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, CAS Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, Uppsala, SE-75124, Sweden.
Small. 2024 Mar;20(13):e2308621. doi: 10.1002/smll.202308621. Epub 2023 Dec 18.
Neuropeptide Y (NPY), as one of the most abundant neuropeptides known, is widely distributed in the central and peripheral nervous system. However, most of the reported NPY-mimetic peptides are hard to cross the blood-brain barrier, target glioma mitochondria, and achieve self-assembly nanostructure in situ. Here, based on the α-helix structure of the novel chiral NPY-mimetic peptides NPY(14), a Y-shaped peptide is designed with the sequences that can be recognized by enterokinase and achieved nanofibers conversion in glioma cell mitochondria. Coupling the Y-shaped NPY-mimetic peptide with the NIR-II fluorophore IR1048, a red-shifting of the fluorescence spectrum beyond 1300 nm is achieved through self-assembly. After the self-assembly in glioma mitochondria, the formed nanofibers can promote intracellular mitochondrial ROS production and extend the NIR-II fluorescence imaging time to at least 7 days in vivo. This work for the first time endows the self-assembly of α-helical-based chiral NPY-mimetic peptides, providing a novel strategy for glioma subcellular regulation enhanced antitumor treatment guided by NIR-II fluorescence imaging.
神经肽 Y（NPY）作为已知最丰富的神经肽之一，广泛分布于中枢和外周神经系统。然而，大多数报道的 NPY 模拟肽难以穿过血脑屏障，靶向神经胶质瘤线粒体，并在原位实现自组装纳米结构。在这里，基于新型手性 NPY 模拟肽 NPY(14)的α-螺旋结构，设计了一种具有可被肠激酶识别的序列的 Y 形肽，并在神经胶质瘤细胞线粒体中实现了纳米纤维的转化。通过自组装，将 Y 形 NPY 模拟肽与近红外二区荧光染料 IR1048 偶联，实现了荧光光谱的红移，超过 1300nm。在神经胶质瘤线粒体中自组装后，形成的纳米纤维可以促进细胞内线粒体 ROS 的产生，并将近红外二区荧光成像时间延长至至少 7 天。这项工作首次赋予了基于α-螺旋的手性 NPY 模拟肽的自组装能力，为近红外二区荧光成像引导的神经胶质瘤亚细胞调控增强抗肿瘤治疗提供了一种新策略。
