適體為單股的DNA或RNA可以透過形成二級結構或三級結構而與目標分子物進行結合，適體模擬了抗體的特性，但比起抗體有更強的專一性及親和性，在臨床上可以用於與致癌基因的結合而達到治療及檢測的用途。Neuropilin-1 (NRP1)是一個細胞膜上的蛋白質，可以促進癌症的形成，包括腫瘤的增生、腫瘤細胞的侵襲性、轉移性及血管新生。由於他細胞質內的結構較短，大多被認為扮演VEGFA165, SEMA3A及其他配體共受體的角色。在非小細胞肺癌患者中發現NRP1的高表現會與病人的低存活率及高腫瘤復發能力相關，在實驗室先前的研究中，已經有針對NRP1蛋白質篩選出專一性高的適體(AP5, AP15, 和 AP37)，雖然這三條適體對於NRP1都有高親和性及專一性的結合，但合成70-80的核甘酸序列用於未來活體實驗上成本仍然是過高，因此我們希望能在這篇研究中優化及縮短與NRP1具有專一性的適體。我們認為縮短的NRP1專一性的適體透過與NRP1結合，可應用於癌症的診斷及治療。本研究我們透過AP5、AP15和AP37的序列製作了一個短適體的微陣列，透過與NRP1的結合，得到幾個與NRP1具有高親和性的短片段適體。第一，我們把有表現NRP1的細胞株與短片段適體進行親和性及專一性的能力分析，證實短片段適體確實會與NRP1有專一性的結合。第二，檢測短片段適體在各種生物功能上的影響，發現短片段的適體不具有細胞毒性，且Ap5-447短片段適體會透過減少絲狀偽足的形成而抑制肺癌細胞的遷移能力，也有抑制細胞侵襲的能力。第三，在3D結構預測中也發現Nrp1專一性適體會纏繞在Nrp1 domain上，透過影響Nrp1蛋白的結構或配體與Nrp1的結合而影響下游訊路徑。第四，Ap5-447適體在動物實驗中也會透過抑制血管新生能力而抑制小鼠腫瘤生長速率，另一方面，我們也在動物體中以同位素的方式去追蹤適體進入體內後的動向，Ap5-447在24小時後能夠專一的貼附在腫瘤微轉移的位置。這個研究表明了NRP1的短片段適體在未來可能會開發成為肺癌的有用的診斷工具及治療策略。

Neuropilin-1 (NRP1) can facilitate cancer progression, including tumor growth, invasion, metastasis and angiogenesis. Non-small cell lung cancer patients with aberrant upregulation of NRP1 have poor disease-free and overall survival rate. In this study, we selected the truncated NRP1-specific aptamers, we found Ap5-447 aptamer inhibited migratory by decreasing filopodia formation, decreasing invasive ability. Intratumoral injection of Ap5-447 aptamer induced a significant decrease in the growth of CL 1-5 xenograft tumors by inhibit angiogenesis. This study revealed that NRP1-specific aptamers might be developed useful diagnostic and therapeutic strategies to lung cancer in the future.

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