Peng Fei, Chen Yongzhu, Liu Jing, Xing Zhihua, Fan Jing, Zhang Wensheng, Qiu Feng
Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China; National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
Periodical Press of West China Hospital, Sichuan University, Chengdu 610041, China.
J Colloid Interface Sci. 2021 Jun;591:314-325. doi: 10.1016/j.jcis.2021.02.019. Epub 2021 Feb 8.
Recently, many kinds of gemini-type amphiphilic peptides have been designed and shown their advantage as self-assembling nanomaterials. In this study, we proposed a simple strategy to design gemini surfactant-like peptides, which are only composed of natural amino acids and can be easily obtained by conventional peptide sythnesis. Taking two prolines as the turn-forming units, a peptide named APK was designed. The petide has a linear sequence but naturally takes the conformation like a gemini surfactant. Compared with a single-tailed surfactant-like peptide A6K, APK showed much stronger ability to undergo self-assembly and to encapsulate hydrophobic pyrene. Several hydrophobic drugs including paclitaxel, doxorubicin, etomidate and propofol were encapsulated by APK, and the corresponding formulations showed anti-tumor or anesthetic efficacy comparable to their respective clinical formulations. Furthermore, APK could inhibit the growth of different microorganisms including E. coli, S. aureus and C. albicans. Etomidate and propofol formulations encapsulated by APK also showed strong antimicrobial activity. Taking APK as an example, our study indicated a straightforward strategy to design gemini surfactant-like peptides, which could be potential nanomaterials for exploring hydrophobic drug formulations with efficacy, safety and self-antimicrobial activity.
最近，多种 Gemini 型两亲性肽已被设计出来，并展现出其作为自组装纳米材料的优势。在本研究中，我们提出了一种设计 Gemini 表面活性剂样肽的简单策略，该肽仅由天然氨基酸组成，可通过常规肽合成轻松获得。以两个脯氨酸作为转角形成单元，设计了一种名为 APK 的肽。该肽具有线性序列，但自然呈现出类似 Gemini 表面活性剂的构象。与单尾表面活性剂样肽 A6K 相比，APK 表现出更强的自组装能力和包封疏水性芘的能力。包括紫杉醇、阿霉素、依托咪酯和丙泊酚在内的几种疏水性药物被 APK 包封，相应制剂显示出与各自临床制剂相当的抗肿瘤或麻醉效果。此外，APK 可抑制包括大肠杆菌、金黄色葡萄球菌和白色念珠菌在内的不同微生物的生长。APK 包封的依托咪酯和丙泊酚制剂也表现出很强的抗菌活性。以 APK 为例，我们的研究表明了一种设计 Gemini 表面活性剂样肽的直接策略，其可能成为探索具有疗效、安全性和自抗菌活性的疏水性药物制剂的潜在纳米材料。
