Oriented Assembly of Cell-Mimicking Nanoparticles via a Molecular Affinity Strategy for Targeted Drug Delivery
Oriented Assembly of Cell-Mimicking Nanoparticles via a Molecular Affinity Strategy for Targeted Drug Delivery
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通过靶向药物输送的分子亲和策略定向组装细胞模拟纳米颗粒
DOI：
10.1021/acsnano.8b09681
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发表时间：
2019
期刊：
影响因子：
17.1
通讯作者：
Li Chong
中科院分区：
文献类型：
--
作者：
Xie Jing;Shen Qing;Huang Kexin;Zheng Tingyu;Cheng Liting;Zhang Zhen;Yu Yang;Liao Guojian;Wang Xiaoyou;Li Chong
细胞膜隐形是药物递送的一个新兴领域，其中母体细胞的特定功能被赋予新形成的仿生载体。越来越多具有不同表面特性的递送系统已被用于该策略，但尚不清楚膜核对的亲和力是否能够保证有效和适当的伪装。在这项研究中，我们提出了一种简洁有效的“分子亲和力”策略，利用跨膜受体的胞内结构域作为膜涂层过程中的“抓手”。采用红细胞（RBC）膜和阳离子脂质体进行制备，并制备源自细胞质蛋白P4.2的肽配体，以特异性识别红细胞关键跨膜受体带3的胞浆结构域。一旦锚定到脂质体表面，P4.2 衍生肽将与分离的红细胞膜相互作用，形成“隐藏肽按钮”，从而确保右侧向外的方向。与传统的聚乙二醇化脂质体相比，膜包被的脂质体表现出约100 nm的适当尺寸分布和高稳定性，具有优异的循环持续时间。重要的是，它们具有通过病原真菌与宿主红细胞之间的相互作用靶向白色念珠菌并中和病原真菌分泌的血毒素的能力。模型药物的疗效因此得到显着提高。总之，“分子亲和力”策略可以为实验室和工业规模的细胞膜涂层生物材料和纳米药物的构建提供强大且通用的方法。
Cell membrane cloaking is an emerging field in drug delivery in which specific functions of parent cells are conferred to newly formed biomimetic vehicles. A growing variety of delivery systems with diverse surface properties have been utilized for this strategy, but it is unclear whether the affinity of membrane–core pairs could guarantee effective and proper camouflaging. In this study, we propose a concise and effective “molecular affinity” strategy using the intracellular domain of transmembrane receptors as “grippers” during membrane coating. Red blood cell (RBC) membranes and cationic liposomes were adopted for fabrication, and a peptide ligand derived from the cytoplasmic protein P4.2 was prepared to specifically recognize the cytoplasmic domain of band 3, a key transmembrane receptor of erythrocytes. Once anchored onto the liposome surface, the P4.2-derived peptide would interact with the isolated RBC membrane, forming a “hidden peptide button”, which ensures the right-side-out orientation. The membrane-coated liposomes exhibited an appropriate size distribution around 100 nm and high stability, with superior circulation durations compared with those of conventional PEGylated liposomes. Importantly, they possessed the ability to targetCandida albicansby the interaction between the pathogenic fungus and host erythrocytes and to neutralize hemotoxin secreted by the pathogenic fungi. The curative effect of the model drug was thus substantially improved. In summary, the “molecular affinity” strategy may provide a powerful and universal approach for the construction of cell membrane-coated biomaterials and nanomedicines at both laboratory and industrial scales.