褐藻酸鈉為水溶性的天然生物高分子，由於無毒性、具有良好的生物相容性(biocompatibility)及生物降解性(biodegradability)，已經過美國食品既藥物管理局(FDA)認可。本研究目標是製備出一含有Fe3O4的褐藻酸鈉/聚氧化乙烯 (Fe3O4-SA/PEO)的奈米纖維膜。以化學共沉澱法合成磁性奈米粒子(Fe3O4)，將其吸附於褐藻酸鈉/聚氧化乙烯(SA/PEO)電紡絲奈米纖維膜，形成一Fe3O4-SA/PEO複合材料。希望能集中四氧化三鐵於腫瘤部位並藉由誘導磁性奈米顆粒產生熱殺死癌細胞，加強癌症之過熱治療效果。
我們使用掃描式電子顯微鏡(SEM)與穿透式電子顯微鏡(TEM)觀察複合材料的纖維形態以及Fe3O4的分佈情形；藉由X光繞射儀(XRD)和超導體量子干涉震動磁量儀(SQUID)，得知複合材料中Fe3O4的結晶結構及具有超順磁特性；以感應耦合電漿質譜分析儀(ICP-MS)儀器測得鐵元素佔整體材料約30%。此外，利用高週波加熱器誘導複合材料產生熱，並發現具有良好的升溫效果。
在細胞實驗方面，以LDH assay及WST-1 test分別測試材料對小鼠大腸直腸癌細胞(CT26)的生物毒性以及體外(in vitro)過熱治療效果。由LDH assay數據顯示，由於材料在第一天會釋放出高濃度的Fe3+或Fe2+，造成約45%的CT26細胞死亡，當培養至第三天，材料對細胞的毒性降低，死亡率與控制組(培養液)相似；在磁場環境中，Fe3O4-SA/PEO被誘導產生熱殺死CT26細胞的效果與純Fe3O4顆粒相近，此過熱治療的結果亦受到Fe3+及Fe2+的影響；因此，未來我們必須改進交聯及氧化鐵合成的方法以降低鐵離子及亞鐵離子的產生，同時也要兼顧纖維的形態。期許未來Fe3O4-SA/PEO材料可以廣泛應用於治療癌症領域。

Sodium alginate is a water-soluble natural biopolymer. Because of its nontoxicity, biodegradability and biocompatibility, it has been approved by FDA. In this study, we prepared a magnetite-sodium alginate/polyethylene oxide (Fe3O4-SA/PEO) nanofibrous mats. Fe3O4 were synthesized by chemical co-precipitation technique and loaded into sodium alginate-based nanofibers which have been electrospun by blending with a biocompatible, synthetic polymer PEO. To enhance hyperthermia effect, the Fe3O4-SA/PEO nanofibrous mats were placed around tumor followed by induction heating by high-frequency AC magnetic induction heater to generate the heat to kill cancer cells.
The morphology of composite and the distribution of Fe3O4 was observed by SEM and TEM micrographs. The results of XRD and SQUID showed the crystalline structure of Fe3O4 and superparamagnetism characteristic. Around 30wt% of Fe were presented in Fe3O4-SA/PEO nanofibrous mat as measured by ICP-MS. Besides, good heating efficiency in Fe3O4-SA/PEO nanofibrous mat was induced in magnetic field.
The cytotoxicity and in vitro hyperthermia effect for CT26 cells were evaluated by LDH assay and WST-1 test, respectively. In LDH test, on the first day, because of high concentration of Fe2+or Fe3+ was released from Fe3O4-SA/PEO, the cell death of this composite was approximate to 45% and it was higher than control group (medium only). However, there was no significant difference between Fe3O4-SA/PEO and control group on the third day. The hyperthermia effect of Fe3O4-SA/PEO was similar to pure Fe3O4 under the AC magnetic field. These results could attributed to the release of Fe2+or Fe3+ during the early cell incubation period. Therefore, it is essential to improve the methods for composite crosslinking as well as magnetite synthesis to decrease the release of iron ions and to ensure that the shape of Fe3O4-SA/PEO nanofibrous mat remained stable in the same time. We believe that Fe3O4-SA/PEO nanofibrous mats have excellent potential as an adjuvant hyperthermia for cancer treatment in the future.

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