国家纳米科学中心乔增莹团队报道了在活细胞线粒体上构建人工壳的偶联诱导组装策略。相关研究成果于2024年7月24日发表在国际顶尖学术期刊《德国应用化学》。

体内自组装策略已经开发出来，用于改善抗癌药物在肿瘤组织中的富集和长期保留。然而，大多数具有非共价键相互作用的自组装容易受到复杂的生理环境的影响，导致稳定性差和生物功能丧失。

该文中，研究人员开发了一种偶联诱导组装（CIA）策略来产生共价交联的纳米纤维，用于在线粒体上原位构建人工外壳。合成了氧化响应肽卟啉偶联物P1，其自组装成纳米颗粒。在线粒体的氧化微环境下，P1中硫醇的偶联导致二聚体的形成，二聚体进一步有序并堆叠成交联的纳米纤维。

因此，由于结合位点的增加，人工外壳通过多价合作相互作用有效地构建在线粒体上。在超声波（US）照射下，壳中的卟啉分子产生大量活性氧（ROS），作用于相邻的线粒体膜，在体外和体内表现出比纳米粒子高约2倍的抗肿瘤活性。因此，线粒体靶向CIA策略为改进声动力疗法（SDT）提供了新的视角，并显示出在抗肿瘤治疗中的潜在应用。

附：英文原文

Title: A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells

Author: Ben-Li Song, Jia-Qi Wang, Guang-Xu Zhang, Ning-Bo Yi, Ying-Jin Zhang, Lei Zhou, Ying-Hua Guan, Xue-Hao Zhang, Wen-Fu Zheng, Zeng-Ying Qiao, Hao Wang

Issue&Volume: 2024-07-24

Abstract: The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.

DOI: 10.1002/anie.202411725

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202411725