【摘要】：本文合成了一種α-環(huán)糊精(α-cyclodextrin,α-CD)與聚酰胺-胺(polyamidoamine,PAMAM)的接枝聚合物(Cy D-G1)。~1H核磁測(cè)試結(jié)果表明,每個(gè)環(huán)糊精分子上平均接枝了6.4個(gè)PAMAM-G1分子。凝膠電泳結(jié)果顯示,Cy D-G1可以有效結(jié)合DNA,并保護(hù)DNA免于核酸酶DNase I的降解。當(dāng)載體與DNA復(fù)合物的N/P比為40時(shí),可以壓縮DNA形成平均粒徑為120 nm左右的粒子,復(fù)合物表面的zeta電位約為+21 m V。該復(fù)合物可以在血清存在的條件下保持粒子的完整性并在360 min內(nèi)穩(wěn)定性良好。與對(duì)照品PEI-25K載體相比,Cy D-G1在高濃度時(shí)仍表現(xiàn)出較低的細(xì)胞毒性。將Cy D-G1與市售Lipofectamine 2000和PEI-25K對(duì)比轉(zhuǎn)染發(fā)現(xiàn),Cy D-G1/DNA復(fù)合物在多種細(xì)胞系中具有較高的轉(zhuǎn)染率,而且轉(zhuǎn)染水平不受血清影響。通過(guò)激光共聚焦觀察并結(jié)合流式細(xì)胞分析表明,該陽(yáng)離子聚合物介導(dǎo)DNA可以在4 h內(nèi)有效進(jìn)入細(xì)胞核內(nèi)。上述結(jié)果證明,該陽(yáng)離子聚合物作為一種非病毒型基因傳遞系統(tǒng)具有優(yōu)良的性能以及體內(nèi)給藥應(yīng)用的潛在可行性。
[Abstract]:A graft polymer (Cy D-G1) of 偽-cyclodextrin (偽-cyclodextrin, 偽-CD) and polyamide-amine (polyamidoamine,PAMAM) was synthesized in this paper. An average of 6.4 PAMAM-G1 molecules were grafted on each cyclodextrin molecule. The results of gel electrophoresis showed that Cy D-G1 could effectively bind to DNA, and protect DNA from degradation of DNase I. When the N / P ratio of the carrier / DNA complex is 40, the DNA can be compressed to form particles with an average particle size of about 120 nm, and the zeta potential on the surface of the composite is about 21 MV. The complex can maintain the integrity of the particles in the presence of serum and has a good stability in the range of 360 min. Compared with PEI-25K vector, Cy D-G1 showed lower cytotoxicity at high concentration. Comparing the transfection of Cy D-G1 with that of Lipofectamine 2000 and PEI-25K, it was found that Cy D-G1/DNA complex had a high transfection rate in many cell lines, and the transfection level was not affected by serum. Laser confocal observation combined with flow cytometry showed that the cationic polymer-mediated DNA could effectively enter the nucleus within 4 hours. These results show that the cationic polymer as a non-viral gene transfer system has excellent performance and potential feasibility of drug delivery in vivo.
【作者單位】： 南方醫(yī)科大學(xué)南方醫(yī)院;廣東藥科大學(xué);中山大學(xué)附屬第一醫(yī)院;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(81373339,81173013)
【分類(lèi)號(hào)】：R914.5

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