利用生物感測器偵測氣喘生物指標-ECP與人類抗癌藥物-cisplatin

Abstract

支氣管上皮細胞上存在的硫酸乙醯肝素 (heparan sulfate) 與類似結構之肝素 (heparin) 對嗜酸性白血球陽離子蛋白 (eosinophil cationic protein，ECP) 有專一及高度的鍵結親合力，實驗利用肝素來當作檢測ECP之探針。先簡單利用定電位安培法將奈米金粒子以電沉積方式修飾在電極表面上，再使用化學合成方法，以半胱胺 (cysteamine) 為鍵結的橋樑，將硫酸乙醯肝素的相似物肝素藉由自組裝的方式修飾至電極上，成功開發了偵測氣喘生物指標 ECP 之電化學生物感測器。實驗室夥伴成功將肝素修飾至金包覆鐵磁性奈米粒子 (Au@Fe3O4 NPs) 上製成功能性磁奈米粒子 (Hep-Au@Fe3O4 NPs)，改善電極偵測 ECP 效果。本研究進一步探討此功能性磁奈米粒子於生物體之應用，最後證實其對細胞無毒，有結合至標靶藥物開發的可能，未來可做更廣泛的應用。 順鉑是治療癌症常使用的藥物，但其造成的副作用往往引起病患相當大的不適，甚至影響肝、腎功能。研究指出，順鉑與鳥嘌呤的鍵結會影響 DNA 雙股結構的形成。實驗利用人體染色體末端重複並含大量鳥嘌呤的DNA序列端粒，結合 SYBR® Green I 嵌入雙股結構後螢光增強的特性，開發出簡單、適用於人體血清並有高靈敏性的螢光分析方式，偵測抗癌藥物順鉑之濃度，期望可應用於藥物研究之領域。

Eosinophil cationic protein (ECP) was used as biomarker for asthma, which was been proved that bound with heparin and heparan sulfate existeded on cell membrane specifically. Based on the specific binding between ECP and heparin and heparan sulfate, gold nanostructured platform was simply formed on the working electrode through controlled electrodeposition, and then, the heparin was immobilized on the gold nanoparticles using the cysteamine as the linker. A electrochemical biosensor for detection of asthma biomarker was developed. other research of our lab improved the detection of ECP by immobilizing heparin on the Au@Fe3O4 NPs. This study further investigated the functional magnetic nanoparticles (Hep-Au@Fe3O4 NPs) in biological applications. We confirmed the functional magnetic nanoparticles are non-toxic and have potential to target drug development. The functional magnetic nanoparticles could be further applied into more extensively usages in the future. Cisplatin is commonly used in chemotherapy. But the side-effects it caused often makes patients discomfortable and even affects their liver and kidney function. Some studies have indicate that the binding between cisplatin and guanine will interfere the formation of DNA double-stranded structure. In this study, we used the telomere of human, a region of repetitive nucleotide sequences that contained a lot of quanine , combining with the character that performing larger fluorescence signal after binding to double-stranded DNA of SYBR ® Green.A simple strategy to sensitively detect cisplatin in human serum have developed. This method may have good prospects for drug research and development field.