Artificial Nanocage Formed via Self-Assembly of β-Annulus Peptide for Delivering Biofunctional Proteins into Cell Interiors
Artificial Nanocage Formed via Self-Assembly of β-Annulus Peptide for Delivering Biofunctional Proteins into Cell Interiors
复制标题
通过 β-环肽自组装形成人工纳米笼，用于将生物功能蛋白递送到细胞内部
DOI：
10.1021/acs.bioconjchem.1c00534
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发表时间：
2022
影响因子：
4.7
通讯作者：
Futaki Shiroh
中科院分区：
文献类型：
--
作者：
Sakamoto Kentarou;Furukawa Hiroto;Arafiles Jan Vincent V.;Imanishi Miki;Matsuura Kazunori;Futaki Shiroh
将功能性蛋白质递送至细胞内部的纳米载体是用于在没有进一步修饰的情况下细胞内递送完整蛋白质的具有体内相容性的有吸引力的平台。需要开发用于货物蛋白包封和在受体细胞胞质溶胶中释放的有效方法。在此，我们评估了使用蛋白质纳米笼（人工纳米笼）的上述要求的可行性，而不损害原始蛋白质的结构和功能，并允许表面和内部的设计灵活性。通过β-环肽（24-氨基酸肽）在水中的自组装形成的蛋白质纳米笼被用作模型框架。在Ni 2+存在下，氨三乙酸部分显示在纳米笼腔上用于六组氨酸标记的蛋白质的有效包封，并且两亲性阳离子裂解肽HAad显示在纳米笼表面上以获得细胞渗透性。通过纳米抗体实现了货物蛋白的成功细胞内递送和胞质蛋白的靶向，表明本研究中采用的方法的有效性。
Nanocarriers that deliver functional proteins to cell interiors are an attractive platform for the intracellular delivery of intact proteins without further modification, with in vivo compatibility. Development of efficient methods for cargo protein encapsulation and release in recipient cell cytosol is needed. Herein, we assess the feasibility of the abovementioned requirements using a protein nanocage (artificial nanocage) without compromising the structure and functions of the original protein and allowing for design flexibility of the surfaces and interiors. The protein nanocage formed via the self-assembly of the β-annulus peptide (24-amino acid peptide) in water was used as a model framework. The nitrilotriacetic acid moiety was displayed on the nanocage lumen for effective encapsulation of hexahistidine-tagged proteins in the presence of Ni2+, and the amphiphilic cationic lytic peptide HAad was displayed on a nanocage surface to attain cell permeability. Successful intracellular delivery of cargo proteins and targeting of cytosolic proteins by a nanobody were achieved, indicating the validity of the approach employed in this study.