载血卟啉单甲醚电荷反转型纳米载体构建及评价

发布时间：2019-07-22 14:18

【摘要】：构建具有电荷反转功能的纳米载体,实现药物的溶酶体逃逸,提高抗肿瘤效果。合成胆固醇-聚乙烯亚胺-六氢邻苯二甲酸酐(Chol-PEI-HHPA)聚合物,利用1H NMR进行结构表征,构建具有电荷反转功能的脂质体(Lipo-HHPA)并负载声敏药物血卟啉单甲醚(HMME),考察Lipo-HHPA-HMME在不同p H条件下的电荷反转情况,利用MCF-7细胞研究载体的溶酶体逃逸及细胞毒性。结果显示,所构建的Lipo-HHPA外观均匀,平均粒径为102 nm,在超声激发下可实现HMME的突释;当pH从7.4变为4.5时,其表面电位由-23.5 mV反转为+21.2 mV;体外细胞实验结果显示,Lipo-HHPA可逃逸溶酶体降解,提高HMME的细胞毒性。以上结果表明,电荷反转型载体有利于增强药物的细胞毒性,提高抗肿瘤效果。
[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.
【作者单位】：宁波市泌尿肾病医院;江苏大学药学院;江西中医药大学;
【基金】：浙江省自然科学基金资助项目(LY14H300001) 国家博士后基金项目(2015M580404,2016T90433) 江苏省博士后基金项目(1402075B)
【分类号】：R943

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