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Sterically Bulky Caging of Transferrin for Photoactivatable Intracellular Delivery
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-07-30 , DOI: 10.1021/acs.bioconjchem.1c00159 Satoshi Yamaguchi 1 , Satoshi Takamori 2 , Kazuho Yamamoto 2 , Akira Ishiwatari 2 , Kosuke Minamihata 3 , Eriko Yamada 1 , Akimitsu Okamoto 1, 2 , Teruyuki Nagamune 2
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-07-30 , DOI: 10.1021/acs.bioconjchem.1c00159 Satoshi Yamaguchi 1 , Satoshi Takamori 2 , Kazuho Yamamoto 2 , Akira Ishiwatari 2 , Kosuke Minamihata 3 , Eriko Yamada 1 , Akimitsu Okamoto 1, 2 , Teruyuki Nagamune 2
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Photoactivatable ligand proteins are potentially useful for light-induced intracellular delivery of therapeutic and diagnostic cargos through receptor-mediated cellular uptake. Here, we report the simple and effective caging of transferrin (Tf), a representative ligand protein with cellular uptake ability, which has been used in the delivery of various cargos. Tf was modified with several biotin molecules through a photocleavable linker, and then the biotinylated Tf (bTf) was conjugated with the biotin-binding protein, streptavidin (SA), to provide steric hindrance to block the interaction with the Tf receptor. Without exposure to light, the cellular uptake of the bTf-SA complex was effectively inhibited. In response to light exposure, the complex was degraded with the release of Tf, leading to cellular uptake of Tf. Similarly, the cellular uptake of Tf-doxorubicin (Dox) conjugates could be suppressed by caging with biotinylation and SA binding, and the intracellular delivery of Dox could be triggered in a light-dependent manner. The intracellularly accumulated Dox decreased the cell viability to 25% because of the cell growth inhibitory effect of Dox. These results provided proof of principle that the caged Tf can be employed as a photoactivatable molecular device for the intracellular delivery of cargos.
中文翻译：
用于光活化细胞内递送的转铁蛋白的空间大体积笼罩
光活化配体蛋白通过受体介导的细胞摄取，可用于光诱导的治疗和诊断货物的细胞内递送。在这里，我们报告了转铁蛋白 (Tf) 的简单有效的笼罩，转铁蛋白是一种具有细胞摄取能力的代表性配体蛋白，已用于各种货物的运输。Tf 通过可光裂解的接头用几个生物素分子进行修饰，然后生物素化的 Tf (bTf) 与生物素结合蛋白链霉亲和素 (SA) 结合，以提供位阻以阻断与 Tf 受体的相互作用。在没有光照的情况下，bTf-SA 复合物的细胞摄取被有效抑制。响应于光照，复合物随着 Tf 的释放而降解，导致细胞摄取 Tf。相似地，Tf-多柔比星 (Dox) 偶联物的细胞摄取可以通过生物素化和 SA 结合的笼养来抑制，并且可以以光依赖的方式触发 Dox 的细胞内递送。由于 Dox 的细胞生长抑制作用，细胞内积累的 Dox 将细胞活力降低至 25%。这些结果提供了原理证明，即笼状 Tf 可用作可光活化的分子装置，用于细胞内货物的递送。
更新日期：2021-08-19
中文翻译：
用于光活化细胞内递送的转铁蛋白的空间大体积笼罩
光活化配体蛋白通过受体介导的细胞摄取，可用于光诱导的治疗和诊断货物的细胞内递送。在这里，我们报告了转铁蛋白 (Tf) 的简单有效的笼罩，转铁蛋白是一种具有细胞摄取能力的代表性配体蛋白，已用于各种货物的运输。Tf 通过可光裂解的接头用几个生物素分子进行修饰，然后生物素化的 Tf (bTf) 与生物素结合蛋白链霉亲和素 (SA) 结合，以提供位阻以阻断与 Tf 受体的相互作用。在没有光照的情况下，bTf-SA 复合物的细胞摄取被有效抑制。响应于光照，复合物随着 Tf 的释放而降解，导致细胞摄取 Tf。相似地，Tf-多柔比星 (Dox) 偶联物的细胞摄取可以通过生物素化和 SA 结合的笼养来抑制，并且可以以光依赖的方式触发 Dox 的细胞内递送。由于 Dox 的细胞生长抑制作用，细胞内积累的 Dox 将细胞活力降低至 25%。这些结果提供了原理证明，即笼状 Tf 可用作可光活化的分子装置，用于细胞内货物的递送。
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