Shang Yuna, Zhu Qingrun, Ding Jiaming, Zhao Liang, Zhang Fan, Lu Jiayi, Feng Yinyin, Wang Jiayu, Liu Zhixue, Kuang Mingjie, Li Chunju
Academy of Interdisciplinary Studies on Intelligent Molecules, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China.
Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
J Control Release. 2024 May;369:75-87. doi: 10.1016/j.jconrel.2024.02.048. Epub 2024 Mar 23.
Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP (P) was selected as the representative of a bioactive peptide. Quaterphen[4]arene (4) exhibited extensive host-guest complexation with P, and the binding constant was (1.16 ± 0.10) × 10 M. In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.
生物活性肽在再生医学和组织工程领域发挥着关键作用。然而，它们在体内和临床中的应用受到其稳定性差、半衰期短和保留率低的阻碍。在此，我们提出了一种使用巨型大环化合物封装生物活性肽的新策略。选择血小板衍生生长因子（PDGF）生物活性模拟肽Nap-FFGVRKKP（P）作为生物活性肽的代表。四苯并[4]芳烃（4）与P表现出广泛的主客体络合作用，结合常数为（1.16 ± 0.10）× 10 M。体外细胞实验证实，P + 4可使骨髓间充质干细胞（BMSC）的增殖提高2.27倍。即使加入抑制剂地塞米松（Dex），P + 4仍能挽救对照组中76.94%的细胞。与Dex组相比，P + 4组骨质疏松小鼠的骨量显著增加。平均小梁厚度（Tb.Th）增加了17.03%，小梁骨体积分数（BV/TV）值增加了40.55%。这种超分子生物活性肽递送策略为递送生物活性肽提供了一种通用方法，并为基于肽的药物开发开辟了新机遇。
