RGD/Dextran/Fe3O4複合奈米粒子於口腔癌之影像標定研究探討

Target study of RGD/Dextran/Fe3O4 composite nanoparticles in Oral cancer image

詹詠晴(Yong-Cing Chan)

指導教授 ： 婁世亮

中原大學/理學院/奈米科技碩士學位學程/碩士(2012年)

https://doi.org/10.6840/cycu201200419

摘要

磁性奈米粒子應用於醫學領域上已成為一項可行的醫學診斷和治療之用途。本研究的主軸為製備具有生物相容性及標定能力之複合奈米粒子，以之獲得MRI及光學影像分析。首先，以共沉澱法合成Dextran/Fe3O4奈米粒子，繼以精氨酸-甘胺酸-天門冬胺酸(RGD)胜肽合成RGD/Dextran/Fe3O4，經由XRD和FT/IR檢測複合奈米粒子的核心為Fe3O4及表面官能基確證表示合成成功；粒子粒徑大小以TEM分析計算約為9.73±4.57 nm；RGD/Dextran/Fe3O4 之SQUID飽和磁化量為16 emu/g。最後於RGD/Dextran/Fe3O4修飾FITC製備最終產物FITC/RGD/Dextran/Fe3O4複合奈米粒子，所製備的奈米粒子分別於小鼠纖維母細胞(L929)及人類口腔麟狀上皮細胞(SCC-4)之生物相容性試驗結果表示FITC/RGD/Dextran/Fe3O4具有良好之生物相容性。於體內及體外試驗之影像探討的結果顯示，複合奈米粒子與口腔腫瘤細胞共培養30分鐘後，可達到磁共振增強顯影效果及螢光影像分析。總言之，本研究成功製備出具備良好生物相容性且具有標定結合能力之複合奈米粒子，經磁共振造影、共軛焦螢光顯微鏡及活體影像系統證實FITC/RGD/Dextran/Fe3O4具有口腔癌腫瘤細胞標定能力，且應用微生物探針可獲取雙重影像之功用，增益醫學診斷之精確度與可信度，進而篩檢口腔癌達到早期診斷及降低再復發可能性。

關鍵字

精氨酸-甘胺酸-天門冬胺酸 ； 人類口腔麟狀上皮細胞 ； 螢光影像 ； 複合奈米粒子 ； 磁共振造影

並列摘要

Magnetic nanoparticles used in the medical field have become a viable diagnosis and treatment mechanism. The purpose of this study is to investigate the preparation and targeting capacity of biocompatible composite magnetic nanoparticles for use in MRI and optical imaging analysis. First, the nanoparticles are synthesized by the co-precipitation method of Dextran/Fe3O4, followed by functionalization with arginine-glycine-aspartic acid (RGD) peptide to form RGD/Dextran/Fe3O4 nanoparticles. Conclusive evidence via XRD and FT/IR detection confirm successful synthesis of Fe3O4 core structure nanoparticles having surface functional groups; the size of particle calculated by TEM analysis is approximately 9.73 ± 4.57 nm. In the case of the RGD/Dextran/Fe3O4 nanoparticles, the SQUID saturation magnetization level is 16 emu/g. The final modification introduces FITC into the RGD/Dextran/Fe3O4 particles forming the end product of FITC/RGD/Dextran/Fe3O4 composite magnetic nanoparticles. The nanoparticles were introduced into mouse fibroblasts (L929) and Human tongue squamous cell carcinoma (SCC-4) for biocompatibility tests, which expressed good biocompatibility between FITC/RGD/Dextran/Fe3O4 nanoparticles and the test sample. Examination of in vivo and in vitro experiments showed that the composite magnetic nanoparticles cultured for 30 minutes with oral tumor cells can enhance MR imaging effects and fluorescence image analysis. In words, this study successfully demonstrates the preparation of composite nanoparticles having good biocompatibility and has an improved calibration of the binding capacity of the composite magnetic nanoparticles. Conjugate focal plane fluorescence microscopy and in vivo imaging systems by magnetic resonance imaging confirmed FITC/RGD/Dextran/Fe3O4 has a targeting ability for oral cancer tumor cells. Applied microbiology probe taking advantage of the dual function of the images improve accuracy and credibility of medical diagnosis, enhancing the ability to screen for oral cancer, increasing the chances of early diagnosis and reducing the possibility of recurrence.

並列關鍵字

Human oral squamous epithelial cells ； Arginine-glycine-aspartic acid ； Composite magnetic nanoparticles ； Magnetic resonance imaging ； Fluorescence imaging

參考文獻

[1] 詹日全, 黃穰基, 潘超群, 王仲祺, 王景平, 劉時安. 口腔癌治療後影響局部復發之相關因素分析. 臺灣耳鼻喉頭頸外科雜誌 2007;42:115-127.

[2] 王宏銘, 廖俊達, 范網行, 吳樹鏗, 詹勝傑, 閣紫宸. 頭頸部鱗狀細胞癌治療的新進展. 腫瘤護理雜誌 2009;9:51-67.

[4] 梁錦榮, 陳大為. 高雄榮總治療上顎口腔癌之臨床分析. Chin J Oral Maxillofac Surg 2004;15:92-98.

[5] 潘怜燕, 邱淑媞. 台灣地區 1991~2007年男女性之健康差距: 以平均餘命, 死亡率及潛在生命年數損失為指標. 臺灣公共衛生雜誌 2011;30:135-149.

[6] 張哲壽. 口腔癌之防治. 聲洋防癌之聲 2007:2-6.