干擾性核醣核酸 (Ribonucleic acid Interference，RNAi)，這個充滿潛力的應用，結合藥物設計將開啟醫療的新紀元。 RNAi 作用場所在細胞膜內，所需克服的首要困難是必須使其具有透膜的特性。正確化學修飾提高 RNAi 的作用分子 siRNA (small interference RNA，siRNA)，其穿過細胞膜低微可能性，保護 siRNA 抵禦酵素的降解的同時也保有釋放效率。相較於現今文獻中結構複雜的多功能載體，本實驗合成出了一個結構相對簡單的載體如 Scheme 1，由聚乙二醇 (Polyethylene glycol，PEG) 和 siRNA 為主體，兩者以具光裂解特性的連結體 (Photocleavable Linker，PL) 相連，其特性是照射 365 nm 波長的光會誘發其斷裂。 此穿膜的載體設計的目的是期望以 PEG 提高載體疏水性及 siRNA 之穩定性；光照斷裂的連結體解決釋放上的調控問題，提高 RNAi 的效率。在沒有陽離子胜肽聚合物或是相反離子 (Counter Ion) 等高分子的協助下，此複合體依然自組裝形成結構完整的圓形粒子，實驗數據結果顯示，GFPsiRNA (Green Fluorescent Protein siRNA) 有機會被攜入進細胞內，抑制目標基因的趨勢。Delivery of small interfering RNA (siRNA) has been one of the major hurdles for the application of RNA interference in therapeutics. The penetration of cell membrane for siRNA still exists the great difficulty. Thus, in order to overcome this challenge, we synthesized a complex with polyethylene glycol (PEG), photocleavable linker (PL), and thiolated siRNA for expecting success in siRNA penetration. Without incorporation of the cationic lipid or polymers with counter ions. PEG-PL-siRNA is still likely to form well-shaped particles. Interestingly, our data shows that those nanocarriers were effectively taken up by cells and then knocked down the expression of GFP gene.
