Spontaneously Right-Side-Out-Orientated Coupling-Driven ROS-Sensitive Nanoparticles on Cell Membrane Inner Leaflet for Efficient Renovation in Vascular Endothelial Injury.
Spontaneously Right-Side-Out-Orientated Coupling-Driven ROS-Sensitive Nanoparticles on Cell Membrane Inner Leaflet for Efficient Renovation in Vascular Endothelial Injury.
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DOI：
10.1002/advs.202205093
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发表时间：
2023-02
期刊：
影响因子：
15.1
通讯作者：
Wu, Wei
中科院分区：
文献类型：
--
作者：
Qin, Xian;Zhu, Li;Zhong, Yuan;Wang, Yi;Wu, Guicheng;Qiu, Juhui;Wang, Guixue;Qu, Kai;Zhang, Kun;Wu, Wei
关键词：
仿生细胞膜伪装技术作为一种可行、有效的方法来实现母细胞纳米粒子的生物学功能，受到了广泛的关注。作为新兴的纳米治疗药物，细胞膜伪装纳米载体的右侧向外定向自组装和病理依赖的“按需”货物释放极大地限制了实际应用的进一步发展。在本研究中，构建了一种自发性右侧向外耦合驱动的 ROS 敏感纳米疗法，通过自发性右侧向外伪装的协同效应来修复靶内皮细胞 (EC)。这种情况是由于细胞膜内叶上关键跨膜受体带 3 的胞内结构域与相应的 P4.2 肽修饰纳米颗粒之间的特异性亲和力造成的，无需额外的共挤出。 “按需”货物释放是由病理性 ROS 可裂解前药引起的。特别是，红细胞伪装纳米治疗药物（RBC-LVTNP）可以通过受损 EC 病灶中的低振荡剪切应力（LSS）血流增强靶向药物输送。体外和体内结果共同证实，RBC-LVTNPs 可以恢复受损的 EC 和功能，恢复血管通透性和低炎症微环境。这些发现为开发仿生细胞膜伪装纳米技术提供了一种强大且通用的方法。通过细胞膜上关键跨膜受体带3的胞内结构域与相应的P4.2肽修饰纳米颗粒之间的特异性亲和力，自发地右侧向外耦合驱动的ROS敏感纳米颗粒无需额外的共挤出，改善了对血管内皮损伤的靶向递送以及由病理性ROS刺激触发的局部“按需”前药激活，从而增强内皮修复。
Biomimetic cell membrane camouflaged technology has drawn extensive attention as a feasible and efficient way to realize the biological functions of nanoparticles from the parent cells. As the burgeoning nanotherapeutic, the right‐side‐out orientation self‐assembly and pathological dependent “on‐demand” cargo release of cell membrane camouflaged nanocarriers remarkably limit further development for practical applications. In the present study, a spontaneously right‐side‐out‐orientated coupling‐driven ROS‐sensitive nanotherapeutic has been constructed for target endothelial cells (ECs) repair through the synergistic effects of spontaneously right‐side‐out‐orientated camouflaging. This condition results from the specific affinity between the intracellular domain of key transmembrane receptors band 3 on cell membrane inner leaflet and the corresponding P4.2 peptide‐modified nanoparticles without the additional coextrusion. The “on‐demand” cargo release results from the pathological ROS‐cleavable prodrug. Particularly, the red blood cell camouflaged nanotherapeutics (RBC‐LVTNPs) can enhance target drug delivery through low oscillatory shear stress (LSS) blood flow in the injured ECs lesion. Both in vitro and in vivo results collectively confirm that RBC‐LVTNPs can restore the damaged ECs and function with the recovered vascular permeability and low inflammation microenvironment. The findings provide a powerful and universal approach for developing the biomimetic cell membrane camouflaged nanotechnology. Spontaneously right‐side‐out‐orientated coupling‐driven ROS‐sensitive nanoparticles through the specific affinity between the intracellular domain of key transmembrane receptors band 3 on the cell membrane and the corresponding P4.2 peptide‐modified nanoparticles without the additional coextrusion, have improved for target delivery to the vascular endothelial injury and local “on‐demand” prodrug activation triggered by the pathological ROS stimulus, thereby enhancing the endothelial repair.
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影响因子：
11.1
作者：
Getzin T;Krishnasamy K;Gamrekelashvili J;Kapanadze T;Limbourg A;Häger C;Napp LC;Bauersachs J;Haller H;Limbourg FP
通讯作者：
Limbourg FP
影响因子：
20.3
作者：
Cheng, Zhongjian;Jiang, Xiaohua;Wang, Hong
通讯作者：
Wang, Hong
影响因子：
39.3
作者：
Costopoulos, Charis;Timmins, Lucas H.;Bennett, Martin R.
通讯作者：
Bennett, Martin R.
DOI：
10.1073/pnas.2103982118
发表时间：
2021-05-25
影响因子：
11.1
作者：
Han, Yue;He, Ming;Chien, Shu
通讯作者：
Chien, Shu
影响因子：
2.7
作者：
Chu W;Guan L;Huang D;Ren Y;Zhou Y
通讯作者：
Zhou Y