"利用表面改質之官能化之聚（3,4-乙烯基二氧噻吩）共聚物製備高靈敏度外泌體感知器平台"

Abstract

外泌體為一種細胞外囊泡，其脂質雙層膜上攜帶多種訊號因子，因此可在細胞間傳遞信號以調控生理和病理機制，使其近年在癌症診斷上的發展受到矚目。在此研究中，我們利用導電高分子聚（3,4-乙烯基二氧噻吩）可透過簡易調控電聚合條件達到奈米結構的特性，成功製備具有奈米結構的官能化聚（3,4-乙烯基二氧噻吩）薄膜作為增強CRC外泌體檢測的生物傳感器。研究數據證實製備的粗糙奈米結構表面可有效改善外泌體檢測的靈敏度，在石英微天秤測量中可測得低至 6.36×109粒子/毫升的靈敏度。除此之外，我們也設計了一種拱橋形的兩性離子多肽鏈，該多肽鏈無論在單一蛋白質溶液或在複雜人體血清中都能有效抵抗非特定性蛋白質的吸附。此兩性離子多肽鏈被用來防止生物分子附著在外泌體傳感平台上，其極低的抗污特性也有助於提高傳感器對外泌體檢測的靈敏度。此研究結果證明了所構建的生物傳感器由於易於製備、便利官能化和極低的非特定性吸附等特性，使其在增強外泌體傳感方面具有出色的潛力。

Exosomes are nanosized extracellular vesicles secreted from most cell types to body fluids. With numerous nucleic acids and various proteins on their lipids, exosomes carrying these characteristic biomolecules act as cargos for intercellular communications. Especially exosomes derived from cancer cells are considered potential biomarkers for early cancer diagnosis. This work successfully fabricated a sensitive exosome biosensor with nanostructured functionalized poly(EDOT) films for enhanced CRC exosome detection. By simply tuning electropolymerization procedures, surface nanostructures of conducting polymers could be easily obtained, and the fabricated rough surfaces showed to improve exosome detection to sensitivities as low as 6.36×109 particles/ml in QCM measurements. On top of that, we designed an arch-like zwitterionic peptide which exhibited superior resistance toward nonspecific adsorption. The zwitterionic peptide was adopted as an antifouling probe on the exosome sensing platform, whose extremely low fouling characteristic also contributed to the sensor’s high sensitivity to exosome detection. These results demonstrated the constructed biosensor’s excellent potential for enhanced exosome sensing due to the facile production, convenient functionalization, and extremely low nonspecific adsorption.