本研究旨在合成出生物相容性高且有助於提升基因傳遞效率之載體，使用一級胺、賴胺酸、芐基半胱胺酸作為材料，經由α-胺基酸N-羧酸酐開環聚合法，成功地合成出帶正電且具有雙親性之線性嵌段聚胺基酸(poly(L-lysine)-b-poly(Benzyl-L-cysteine)，PLL-b-PBLC)，並將賴胺酸改質得到胍化之線性嵌段聚胺基酸(Guanidinylation of PLL-b-PBLC，PLGL-b-PBLC)，期待可與帶負電的基因藉由靜電作用力而複合，且易吸附於同樣帶負電的細胞膜，再透過疏水鏈段以及胍基提升複合粒子被細胞攝入體內的機會。以不同成分、聚合度以及嵌段聚合比例設計出不同性質的基因載體。透過1H NMR分析聚胺基酸之聚合度與分子量，而後再經由13C NMR、FT-IR、CD、FL、SAXS鑑定聚胺基酸之改質基團、二級結構、開始聚集濃度、聚集微結構，聚胺基酸之粒徑則是以TEM分析。確立聚胺基酸之基本性質後開始檢驗其溶血性與細胞毒性，以得知聚胺基酸是否具備生物相容性與細胞活性，從結果篩選出PLL10-b-PBLC5、PLL5-b-PBLC5、PLGL5-b-PBLC5執行後續實驗。測定聚胺基酸與基因之複合粒子之Zeta potential以篩選出適當N/P ratio範圍進行轉染，首先以聚胺基酸複合LacZ基因做轉染測試，從結果可以發現複合粒子有助於提升基因傳遞效率，成功建立起轉染系統並應用於p53基因轉染測試，於Cisplatin環境下若細胞含有p53基因將會大量死亡，故以添加Cisplatin前後之細胞存活率檢驗成功表達p53之細胞比例，結果指出N/P ratio 8 PLL10-b-PBLC5與N/P ratio 24 PLL5-b-PBLC5乃最有效提升基因傳遞效率，證實其具有基因載體發展之潛力。

In this study, we develop a series of linear block copolypeptides, that are low toxicity and low hemolysis, as gene carriers. Poly(L-lysine)-block-poly(L-benzyl-cysteine) serves as our polypeptide carrier that is applied to gene therapy. We select the polypeptides with high gene expression through adjusting the structures and properties of polypeptides by varying composition, chain length, and block ratio. The hydrophobic group on the polypeptides could not only reduce toxicity but also enhance cellular uptake due to its non-specific interaction with the cell membrane. The positively charged polypeptides can complex with negatively charged pDNA via electrostatic interactions to form gene carriers. Properties and conformation of polypeptides were confirmed by 1H NMR, 13C NMR, FT-IR and circular dichroism (CD) spectroscopy, pointing out that we successfully synthesized these polypeptides. Investigation of hemolysis and cell viability assays indicated these polypeptides can be great candidates for biomaterial applications. We transfected p53 into cell after using LacZ as reported gene to make sure that these polypeptides can be the candidates of gene carriers, and the results proved complexes succeeded in transfecting DNA.

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