利用奈米金粒子與鈣離子建構之電荷交聯法增加胜肽超分子水膠機械穩定性之研究

Abstract

胜肽超分子水膠由於具有獨特之生物活性，生物功能性和生物相容性，已經被廣泛地研究於生醫材料領域。然而，其有機組成物之結構往往使得胜肽超分子水膠具有較低之機械穩定性。為了擴大胜肽超分子水膠之實用性與應用領域，發展胜肽超分子水膠之仿生材料以及增加機械穩定性扮演著關鍵性的角色。在此，我們提出一種創新電荷交聯法，利用Naphthyl-Phe-Phe-Cys (NapFFC)寡肽，與奈米金粒子(AuNPs)和鈣離子(Ca2+)結合所形成之胜肽超分子水膠。其中機械穩定性之提高是由於胜肽多聚體之形成，通過與奈米金粒子連接和鈣離子誘導之聚集，所產生之密集纏結纖維網狀結構。利用穿透式電子顯微鏡(TEM)，掃描式電子顯微鏡(SEM)圖像和傅里葉轉換紅外光譜(FT-IR)的分析，我們釐清了奈米纖維網狀結構之型態以及水凝膠之結合作用力。光學圖像，紫外光光譜(UV-Vis)和螢光分光光度計之分析也顯示了在各種溶劑中水膠對溶劑之耐侵蝕性明顯地被增強了。這些結果均顯示了奈米金粒子與鈣離子可以增強NapFFC之奈米纖維兩倍以上之厚度，此現象可以形成更強之網狀結構以及減少水膠組成物釋放量。我們更進一步用實驗證實，作為一個仿生材料，NapFFC-AuNPs所形成之胜肽超分子水膠可以讓Hela細胞生長於其上，並且具有高度的細胞存活率，以及細胞只有觸碰到包覆藥物之水膠才會死亡。我們預計這種電荷交聯方法之胜肽超分子水膠具有大為改善之機械穩定性，將被作為一個合適之藥物載體用於癌症手術後之水膠敷料，防止癌細胞轉移。

Peptide-based supramolecular hydrogels have been comprehensively investigated in biomaterials applications due to their unique bioactive, biofunctionality, and biocompatible features. However, the presence of organic building blocks often makes peptide-based hydrogels have low mechanical stability. In order to expanding their practicality and application field, it is promising to develop the tool kits for the bioinspired materials of peptide-based supramolecular hydrogels and improve their mechanical stability. Here, we present an innovative charge-cross-linking approach using Naphthyl-Phe-Phe-Cys (NapFFC) oligopeptides, combined with the gold nanoparticles (AuNPs) and calcium ions (Ca2+) forming peptide-based supramolecular hydrogels. The enhancement of the mechanical stability was due to the densely entangled fibrous network of peptide multimer through AuNPs linkage and Ca2+ induced agglomeration. The morphology of nanofibrous network constructions and the binding forces of hydrogel were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM) image and Fourier transform infrared spectroscopic (FT-IR). The optical image, UV-Vis spectra and fluorescence spectrophotometer analysis were also studied to show the stability enhancement of solvent erosion resistance in various solvents. All of these results indicated that AuNPs and Ca2+ can strengthen more than twice as much diameter of NapFFC nanofiber thickness which can form stronger frameworks and reduce released amount of components. Our further experiments confirmed that Hela cells can grow on the NapFFC-AuNPs hydrogel with high cell viability as a bioinspired material and the cells could be dead as touching the drug-inclusive hydrogel. We expected that this charged-cross-linked method and peptide-based supramolecular hydrogels with much improved mechanical stability will be used as a favorable drug carrier for hydrogel dressings after cancer surgery to prevent metastasis.