Natural Polyphenols Augment Cytosolic Protein Delivery by a Functional Polymer
Natural Polyphenols Augment Cytosolic Protein Delivery by a Functional Polymer
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DOI：
10.1021/acs.chemmater.8b04672
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发表时间：
2019-03-26
影响因子：
8.6
通讯作者：
Cheng, Yiyun
中科院分区：
文献类型：
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作者：
Liu, Chongyi;Shen, Wanwan;Cheng, Yiyun
胞浆蛋白递送对于基础细胞生物学和基于蛋白质的新型生物疗法的发现具有重要意义。这仍然是一个具有挑战性的任务，因为蛋白质上的结合位点有限，而且它们的大小相对较大。因此，目前大多数胞浆蛋白输送方法需要对天然蛋白质进行共价修饰，这通常涉及复杂的合成、降低蛋白质的生物活性以及意外的安全性问题。在这项研究中，我们提出了一种新的策略，通过对天然多酚和含硼酸聚合物的特定识别来传递不同分子尺寸和等电点的蛋白质。蛋白质分子通过非共价氢键/疏水作用或可逆的动态共价键与多酚进行修饰。天然多酚增加了蛋白质与含硼酸聚合物之间的结合亲和力，由于邻苯二酚-硼酸酯的pH敏感性，使结合的蛋白质能够在酸性环境中释放，从而极大地提高了细胞质的递送效率。该策略在运送牛血清白蛋白、藻红蛋白和核糖核酸酶A等多种蛋白质方面表现出了强劲的效率，并在细胞内释放后保持了蛋白质的生物活性。报道的策略允许开发一种多酚参与的聚合物平台，用于胞浆蛋白输送。
Cytosolic protein delivery is of great importance for basic cell biology and the discovery of novel protein-based biotherapeutics. It remains a challenging task because of the limited binding sites on proteins and their relatively large size. As a result, most current approaches for cytosolic protein delivery need covalent modification on native proteins, which is usually involved with complicated synthesis, reduced protein bioactivity, and unexpected safety concerns. In this study, we proposed a novel strategy to deliver proteins of different molecular sizes and isoelectric points by specific recognitions between natural polyphenols and boronic acid-containing polymers. Protein molecules were decorated with polyphenols via noncovalent hydrogen-bond/hydrophobic interactions or reversible dynamic covalent bonds. The natural polyphenols increase the binding affinity between proteins and boronic acid-containing polymers, allow the release of bound proteins in acidic environments because of pH-sensitive property of catechol-boronate esters, and thus greatly promote the cytosolic delivery efficiency. This strategy showed robust efficiency in the delivery of various proteins such as bovine serum albumin, phycoerythrin, and ribonuclease A and maintained the protein bioactivity after intracellular release. The reported strategy permits the development of a polyphenol-involved polymer platform for cytosolic protein delivery.