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本研究制备了一种纳米载药系统,通过对几种化学或基因药物的同时递送,实现多种药物的协同效应或降低肿瘤对药物的耐药性,从而达到提高肿瘤治疗的目的。在本研究中,通过考察粒径分布及载药量对不同的阳性脂材进行筛选,成功制备可以同时传递阴离子小干扰RNA(siRNA)和化疗药物多西他赛的阳性纳米脂质载体(cNLC)。同时,利用能与肝癌细胞表面特异性结合的新型肽SP94对cNLC的表面进行修饰,最终制得具有主动靶向功能的cNLC。琼脂糖凝胶色谱结果显示制得的cNLC可以有效的装载siRNA。超滤离心法去除游离药物后,HPLC图谱显示cNLC能够高效的包载多西他赛。与市售制剂泰索帝相比,制得的SP94-cNLC显示出更强的细胞毒性,这表明SP94修饰的cNLC能更高效的递送多西他赛进入肝癌细胞。而在姜黄素和多西他赛共载的NLC中,通过姜黄素对多西他赛的敏化作用提高多西他赛在侵袭性癌细胞中的细胞毒性,这种共载系统能够改善化疗药物单独使用时疗效较差的缺点。
This study prepared a nano-drug delivery system, through the simultaneous delivery of several chemical or genetic drugs to achieve synergistic effects of various drugs or reduce the tumor drug resistance, so as to achieve the purpose of improving cancer treatment. In this study, we successfully prepared positive nanoliposomes (cNLCs) that can simultaneously deliver small interfering RNA (siRNA) and docetaxel chemotherapeutic drugs by screening different positive lipid materials by investigating the particle size distribution and drug loading. ). At the same time, the surface of cNLC was modified with a new peptide SP94 that can specifically bind to the surface of liver cancer cells, finally cNLC with active targeting function was obtained. Agarose gel chromatography results show that the prepared cNLC can effectively load siRNA. After ultrafiltration centrifugation to remove free drug, the HPLC chromatogram showed that cNLC could effectively encapsulate docetaxel. The prepared SP94-cNLC showed more cytotoxicity than the commercially available formulation, taxotere, indicating that SP94-modified cNLC can deliver docetaxel more efficiently into liver cancer cells. In NLC curcumin and docetaxel, however, sensitization of docetaxel to curcumin improves the cytotoxicity of docetaxel in invasive cancer cells in a co-loaded system that improves chemotherapy The shortcomings of poor efficacy of drugs when used alone.