Interests in intracellular peptide delivery have continued to grow, significantly fueled by the importance of peptides and their mimetics in modern cell biology and pharmaceutical industry. However, efficient intracellular delivery of membrane-impermeable peptides of different polarities remains a challenging task. In this study, we develop a general and robust strategy for intracellular peptide delivery by using a boronic acid-rich dendrimer. The designed material is capable of transporting peptides with different polarities and charge properties into the cytosol of various cell lines without inducing additional cytotoxicity. The transduction efficacy and proteolytic stability of cargo peptides delivered by the boronic acid-rich dendrimer are much superior to peptides conjugated with cell penetrant peptides such as octaarginine. In addition, the bioactivities of pro-apoptotic peptides are maintained after intracellular delivery. This study provides a versatile and robust platform for the intracellular delivery of membrane-impermeable peptides.

肽及其模拟物在现代细胞生物学和制药行业中的重要性极大地推动了细胞内肽递送的兴趣不断增长。然而，不同极性的膜不可渗透肽的有效细胞内递送仍然是一项艰巨的任务。在这项研究中，我们通过使用富含硼酸的树状大分子，开发了一种用于细胞内肽递送的通用且可靠的策略。设计的材料能够将具有不同极性和电荷特性的肽转运到各种细胞系的细胞质中，而不会引起额外的细胞毒性。富含硼酸的树状大分子传递的货物肽的转导效率和蛋白水解稳定性远优于与细胞渗透肽（例如八精氨酸）缀合的肽。此外，细胞内递送后，前凋亡肽的生物活性得以维持。这项研究为膜内不透性肽的细胞内递送提供了一个通用而强大的平台。