製備一結合氧化鐵奈米粒子與超分水膠之新穎生醫材料並以磁場刺激控制藥物釋放

Abstract

近年來，由於磁性水膠具有可操控與可有效刺激的特性，並且在許多領域都可以被廣泛應用，使得它成為一種新興的生物複合材料。在本篇研究中，我們開發了一種由超分子水膠結合奈米氧化鐵粒子所製備而成的傷口敷料，這個奈米複合物具有良好的生物相容性以及對外在刺激敏感的特性，因此被視為一種新穎的生物材料，而其優越的反應能力與可被調控的可行性特別適用於藥物釋放的應用。這種獨特的超分子水膠是由2-Naphthylacetic acid (Nap)和diphenylalanine (FF) 胜肽所組成，他們可藉由自組裝的方式結合形成纖維網狀結構；而鐵奈米粒子是由共沉澱法合成的，因為合成條件單純且溫和，所製備出來的鐵奈米粒子非常適合用於生醫應用上。藉由光學圖像及掃描式電子顯微鏡影像可以證明鐵奈米粒子的加入有助於提升Nap-FF凝膠因子的成膠性質。接下來，為了測試藥物釋放的表現，fluorescein isothiocyanate (FITC)和doxorubicin (DOX)分別被裝載進水膠中，利用高頻交流磁場可促使藥物從水膠中釋放出來。這是因為在交流磁場下，磁性氧化鐵核因感應磁場而產生熱能，使得水膠加速被瓦解而釋放出大量的藥物；相較於擴散釋放機制，藉由施加外在磁場可以使藥物更快更有效率的被釋放，經由控制磁場之開關亦可達成按需給予的間歇性釋放。進一步地，為了驗證此種材料在醫療領域的發展性，我們將Nap-FF-Fe3O4水膠對海拉細胞做了細胞毒性的測試，結果顯示當它們被作為固態之傷口敷料時，它們不但表現出很良好的生物相容性，並且藉由磁場釋放的DOX藥物分子也可以有效的殺死癌細胞。根據上述的結果，這個生醫材料Nap-FF-Fe3O4被應用於傷口敷料的製作是可以期待的，且利用水膠做為藥物載體並結合磁場釋放的機制，可以使藥物更有效的被利用。

Recently, magnetic hydrogels have emerged as a novel biocomposite for their controllability, active response properties and extended applications. In this study, we have developed Fe3O4 nanoparticles-incorporated supramolecular hydrogels as wound dressings. This nanocomposite was biocompatible and sensitive to external stimuli, which can be used as a novel biomaterial for drug delivery with superior response and feasibility to be controlled. The unique supramolecular hydrogelators composed of 2-Naphthylacetic acid (Nap) and diphenylalanine peptides (FF) were able to self-assemble together and form fibrous networks. The Fe3O4 nanoparticles synthesized by co-precipitation method were suitable for biomedical applications because of the simple and mild synthetic conditions. The optical images and scanning electron microscope (SEM) images demonstrated that the gelation property of the Nap-FF hydrogelator can be enhanced by addition of Fe3O4 nanoparticles. Next, for drug delivery purpose, fluorescein isothiocyanate (FITC) and doxorubicin (DOX) were separately loaded in the hydrogels. A high frequency alternating magnetic field (AMF) was used to trigger the drug release from the hydrogels. This is because application of AMF resulted in the heating within the nanocomposites leading to accelerated collapse and squeezing out large amounts of imbibed drug. In comparison with the diffusion mechanism, drugs can be released faster and more efficiently by applying external magnetic field. On-demand pulsatile drug release can be achieved by application of external magnetic stimulation. Furthermore, in order to validate the development of this material in the medical uses, the cytotoxicity test against HeLa cell line was applied on the Nap-FF-Fe3O4 hydrogels. The results supported that not only their outstanding biocompatibility were performed when used as solid wound dressings but the DOX molecules released from the nanocomposites by magnetic stimulation can effectively kill the cancer cells. Based on the results, the biomaterials, Nap-FF-Fe3O4 hydrogels, are promising materials for wound dressings and drugs in the hydrogels can be used in a more effective way with the assistance of the external magnetic field.