ABSTRACT Herein, we develop a switchable peptide-equipped protein/cucurbit[7]uril (CB[7]) supramolecular assembly as novel targeted drug vector. Specifically, bovine serum albumin (BSA) is used to interact with CB[7], serving as the core of drug vector. Then, a peptide shield layer is formed on the surface of BSA/CB[7], yielding peptide-equipped supramolecular assembly (Pep@BSA@CB[7]). The equipped peptide shield layer is composed of switchable peptide probes consisting of a polycationic cell-penetrating peptide (CPP) motif, a polyanionic motif and a linking motif, and therefore provides a variety of desirable properties. First, the CPP motif displays excellent cell penetration ability and can facilitate internalisation of the drug vector. Secondly, the polyanionic motif performs intramolecular electrostatic interaction with CPP motif and thereby can reduce non-targeted delivery towards normal cells. Thirdly, the linking motif can be specifically cleaved by matrix metalloproteinases 2 that is up-regulated in tumour microenvironment, thus enabling precise cancer-targeting. As a consequent, Pep@BSA@CB[7] can serve as a promising drug vector that exhibits superior targeting ability and high uptake efficiency towards cancer cells, which may be of great potential in cancer-targeted treatment. GraphicalAbstract

中文翻译：

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用于靶向药物递送的可切换肽装备蛋白/葫芦[7]uril超分子组装

摘要在此，我们开发了一种可转换的肽装备蛋白/葫芦[7] uril (CB[7]) 超分子组装作为新型靶向药物载体。具体而言，牛血清白蛋白（BSA）用于与CB[7]相互作用，作为药物载体的核心。然后，在 BSA/CB[7] 的表面形成肽屏蔽层，产生带有肽的超分子组装体（Pep@BSA@CB[7]）。配备的肽屏蔽层由可切换的肽探针组成，该探针由聚阳离子细胞穿透肽 (CPP) 基序、聚阴离子基序和连接基序组成，因此提供了各种理想的特性。首先，CPP 基序显示出优异的细胞渗透能力，可以促进药物载体的内化。第二，聚阴离子基序与 CPP 基序进行分子内静电相互作用，从而减少对正常细胞的非靶向递送。第三，连接基序可以被在肿瘤微环境中上调的基质金属蛋白酶 2 特异性切割，从而实现精确的癌症靶向。因此，Pep@BSA@CB[7] 可以作为一种很有前景的药物载体，对癌细胞表现出优异的靶向能力和高吸收效率，在癌症靶向治疗中可能具有巨大潜力。图形概要 Pep@BSA@CB[7] 可以作为一种很有前景的药物载体，对癌细胞表现出优异的靶向能力和高吸收效率，在癌症靶向治疗中可能具有巨大潜力。图形概要 Pep@BSA@CB[7] 可以作为一种很有前景的药物载体，对癌细胞表现出优异的靶向能力和高吸收效率，在癌症靶向治疗中可能具有巨大潜力。图形概要