Vilaça Helena, Castro Tarsila, Costa Fernando M G, Melle-Franco Manuel, Hilliou Loic, Hamley Ian W, Castanheira Elisabete M S, Martins José A, Ferreira Paula M T
Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
J Mater Chem B. 2017 Nov 21;5(43):8607-8617. doi: 10.1039/c7tb01883e. Epub 2017 Oct 27.
Peptide-based self-assembled hydrogels have triggered remarkable research interest in recent years owing to their biocompatibility and biomimetic properties and responsiveness, which warrant many technological and biomedical applications. Dehydrodipeptides N-capped with naproxen emerged from our research as effective hydrogelators endowed with resistance to proteolysis. Dehydrodipeptide-based hydrogels are promising nanocarriers for drug delivery applications. In this work, we demonstrate that dehydrodipetide Npx-l-Ala-Z-ΔPhe-OH can be deployed as a minimalist hydrogelator module for synthesizing a gelating construct Npx-l-Ala-Z-ΔPhe-G-R-G-D-G-OH bearing a GRGDG adhesion motif. The self-assembly of the peptide construct and the drug delivery properties of the hydrogel were studied in this work. The peptide construct showed no toxicity towards a fibroblast cell line expressing the αβ integrin. Docking studies suggest that the hydrogelator block does not interfere with the recognition of the RGD motif by the integrin receptor. The self-assembly seems to be directed by intermolecular naphthalene π-π stacking interactions, with the peptide backbone assuming a random coil conformation both in solution and in the gel phase. TEM and STEM imaging revealed that the hydrogel is made of entangled bundles of long thin fibres (width circa 23 nm). The hydrogel exhibits viscoelastic properties, thermo-reversibility and recovery after mechanical fluidization. FRET studies showed that curcumin incorporated into the hydrogel interacts non-covalently with the hydrogel fibrils. Delivery of curcumin from the hydrogel into Nile red loaded model membranes (SUVs) was demonstrated by FRET. Naproxen N-capped dehydrodipeptides are efficacious minimalist hydrogelator modules for obtaining hydrogels functionalized with peptide ligands for cell receptors. These hydrogels are potential nanocarriers for drug delivery.
近年来，基于肽的自组装水凝胶因其生物相容性、仿生特性和响应性而引发了显著的研究兴趣，这些特性使其在许多技术和生物医学应用中具有价值。我们的研究发现，用萘普生N-封端的脱氢二肽是有效的水凝胶剂，具有抗蛋白水解能力。基于脱氢二肽的水凝胶是用于药物递送应用的有前景的纳米载体。在这项工作中，我们证明脱氢二肽Npx-l-Ala-Z-ΔPhe-OH可作为一种极简水凝胶剂模块，用于合成带有GRGDG粘附基序的凝胶化构建体Npx-l-Ala-Z-ΔPhe-G-R-G-D-G-OH。本文研究了该肽构建体的自组装以及水凝胶的药物递送特性。该肽构建体对表达αβ整合素的成纤维细胞系无毒性。对接研究表明，水凝胶剂模块不会干扰整合素受体对RGD基序的识别。自组装似乎是由分子间萘的π-π堆积相互作用引导的，肽主链在溶液和凝胶相中均呈无规卷曲构象。透射电子显微镜（TEM）和扫描透射电子显微镜（STEM）成像显示，水凝胶由长细纤维缠结束组成（宽度约为23 nm）。该水凝胶具有粘弹性、热可逆性以及机械流化后的恢复能力。荧光共振能量转移（FRET）研究表明，掺入水凝胶中的姜黄素与水凝胶原纤维非共价相互作用。通过FRET证明了姜黄素从水凝胶向负载尼罗红的模型膜（小单层囊泡，SUVs）的递送。萘普生N-封端的脱氢二肽是用于获得用细胞受体肽配体功能化的水凝胶的有效极简水凝胶剂模块。这些水凝胶是药物递送的潜在纳米载体。
