發(fā)布時(shí)間：2019-07-22 14:18

【摘要】：構(gòu)建具有電荷反轉(zhuǎn)功能的納米載體,實(shí)現(xiàn)藥物的溶酶體逃逸,提高抗腫瘤效果。合成膽固醇-聚乙烯亞胺-六氫鄰苯二甲酸酐(Chol-PEI-HHPA)聚合物,利用1H NMR進(jìn)行結(jié)構(gòu)表征,構(gòu)建具有電荷反轉(zhuǎn)功能的脂質(zhì)體(Lipo-HHPA)并負(fù)載聲敏藥物血卟啉單甲醚(HMME),考察Lipo-HHPA-HMME在不同p H條件下的電荷反轉(zhuǎn)情況,利用MCF-7細(xì)胞研究載體的溶酶體逃逸及細(xì)胞毒性。結(jié)果顯示,所構(gòu)建的Lipo-HHPA外觀均勻,平均粒徑為102 nm,在超聲激發(fā)下可實(shí)現(xiàn)HMME的突釋;當(dāng)pH從7.4變?yōu)?.5時(shí),其表面電位由-23.5 mV反轉(zhuǎn)為+21.2 mV;體外細(xì)胞實(shí)驗(yàn)結(jié)果顯示,Lipo-HHPA可逃逸溶酶體降解,提高HMME的細(xì)胞毒性。以上結(jié)果表明,電荷反轉(zhuǎn)型載體有利于增強(qiáng)藥物的細(xì)胞毒性,提高抗腫瘤效果。
[Abstract]:The nanometer carrier with charge reversal function was constructed to realize the escape of lysosome and improve the antitumor effect. Cholesterol-polyethylene imine-hexahydrophthalic anhydride (Chol-PEI-HHPA) polymer was synthesized and characterized by 1H NMR. The liposomes with charge reversal function (Lipo-HHPA) were constructed and the charge inversion of Lipo-HHPA-HMME under different pH conditions was investigated by loading the sound sensitive drug hematoporphyrin monomethyl ether (HMME),. The lysosome escape and cytotoxicity of the vector were studied by MCF-7 cells. The results showed that the appearance of the constructed Lipo-HHPA was uniform, and the average particle size of nm, could realize the sudden release of HMME under ultrasonic excitation, and the surface potential of pH changed from-23.5 mV to 21.2 mV; in vitro. The results showed that Lipo-HHPA could escape lysosome degradation and improve the cytotoxicity of HMME. These results suggest that the charge reverse transformation vector is beneficial to enhance the cytotoxicity of the drug and improve the antitumor effect.
【作者單位】： 寧波市泌尿腎病醫(yī)院;江蘇大學(xué)藥學(xué)院;江西中醫(yī)藥大學(xué);
【基金】：浙江省自然科學(xué)基金資助項(xiàng)目(LY14H300001) 國(guó)家博士后基金項(xiàng)目(2015M580404,2016T90433) 江蘇省博士后基金項(xiàng)目(1402075B)
【分類號(hào)】：R943

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