金奈米粒子因具有特別的物理及化學特性，在專一性的標靶治療之藥物運送中扮演了重要的角色。複合上生物性的抗原或抗體、光學感應器、疾病或癌症治療的藥物的金奈米複合物被廣泛的應用在生物體上。肺臟微血管內皮細胞上的 Dipeptidyl peptidase IV (DPP IV) 和癌細胞表面組裝的纖連蛋白 fibronectin (FN) matrix 兩者之間的結合，在癌症肺臟轉移的過程中扮演重要的角色。研究指出，DPP IV 的片段蛋白，DP4A，是主要與 FN 結合的區域並且具有潛力阻斷因 DPP IV 和 FN 作用而造成的癌症轉移現象。基於 DP4A 的特異性，我們利用金奈米粒子作為載體，製備出 DP4A 複合的金奈米粒子 DP4A-AuNP 複合物，並且探討此材料之特性及其在 in vitro 及 in vivo 中所帶來的影響。首先，在探討 DP4A 在與金奈米粒子複合前後差異的過程中，我們發現 DP4A-AuNP 複合物與 FN 的 Kd 值 (解離常數) 比起相同劑量下 free DP4A 與 FN 的 Kd 值約有九倍的差異，顯示 DP4A 複合金奈米粒子之後對於 FN 的親和力大幅的提升，同時我們也透過 DPP IV binding assay 進一步證實 DP4A-AuNP 複合物的確具有較好的能力去阻斷 DPP IV 與 FN 之間的結合。In vitro，利用 4T1 及 LL2 兩株具有肺臟轉移能力的癌細胞進行細胞黏附實驗發現 DP4A-AuNP 複合物相較於 free DP4A 可以更有效的降低細胞黏附能力。In vivo 方面，我們發現 DP4A-AuNP 複合物也有明顯抑制癌細胞肺臟轉移的效果。綜合以上實驗結果，我們發現將 DP4A 複合上金奈米材料之後，不僅在 in vitro 可以有效的提高對於 FN 的親和力並降低癌細胞的黏附能力，另外，在 in vitro 方面 DP4A-AuNP 複合物也同時具有抑制癌細胞肺臟轉移的效果。這樣的金奈米複合材料可望在未來進一步攜帶藥物並專一性針對癌細胞作用，進而達到抑制癌症轉移的目的。

Gold nanoparticles (AuNPs) have been extensively used as agents of target-specific delivery therapy due to their unique chemical and physical properties for transporting and loading the pharmaceutics, especially when conjugated with biological ligands or antibody, optical sensing, and therapeutic drugs for various diseases. In lung metastasis, the blood-borne cancer cells become arrested in the lung vasculature via the adhesion between DPP IV and pericellular polymetric fibronectin (polyFN). Further studies indicated that the portion of the DPP IV, named DP4A, is the major FN-binding domain and has the potential to block DPP IV/FN-mediated adhesion and metastasis. According to the specificity of DP4A, we developed a novel form of DP4A that is bound to a carrier in the nanometer scale and further examined its properties in vitro and in vivo. After conjugating DP4A with AuNPs, this complex had approximately nine-fold Kd value lower than free DP4A and also blocked the binding between DPP IV and FN. In vitro, cell adhesion assay showed that DP4A-AuNP complex had higher suppressive effects on cell adhesion in both 4T1 and LL2 cells than free DP4A. In vivo, DP4A-AuNP complex also enhanced the inhibitory effect of DP4A on lung metastasis. In conclusion, our results demonstrate that utilizing nanomaterial as a carrier to conjugate proteins appears to enhance their biological functions. The DP4A-AuNP complex is expected to carry drugs and specifically target cancer cells as a strategy to prevent cancer metastasis.

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洪婷婷 (2007)。定位大鼠第四型雙肽蛋白水解酶其細胞外區域中之纖連蛋白基質及單株抗體6A3的結合位點。國立成功大學碩士論文。

劉如芳 (2009)。一段DPP Ⅳ 胜肽結合到轉移性癌細胞表面上之Fibronectin Matrix 的後果。國立成功大學碩士論文。