Abstract：
Cancer is one of the most lethal diseases all over the world. Despite that many drugs have been developed for cancer therapy, they still suffer from various limitations including poor treating efficacy, toxicity to normal human cells, and the emergence of multidrug resistance. In this study, the amphiphilic LHES polymers were prepared using hydroxyethyl starch (HES) and linoleic acid as starting materials. The content and substitution degree of linoleic acid groups in LHES polymers were analyzed. The LHES polymers were used for fabricating LHES-B nanoparticles carrying a linoleic acid modified berberine derivative (L-BBR). The LHES-B nanoparticles showed high drug loading efficiency (29%) and could quickly release L-BBR under acidic pH condition (pH = 4.5). Biological investigations revealed that LHES-B nanoparticles significantly inhibited the proliferation of HepG2 cells and exhibited higher cytotoxicity than L-BBR. In a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasv12) zebrafish model, LHES-B nanoparticles obviously inhibited the expression of krasv12 oncogene. These results indicated that LHES carriers could improve the anticancer activity of L-BBR, and the synthesized LHES-B nanoparticles showed great potential as anticancer drug.
摘要：
癌症是世界上最致命的疾病之一。尽管已经开发了许多用于癌症治疗的药物，他们仍然受到各种限制，包括治疗效果差，对正常人细胞的毒性，以及多药耐药性的出现。在这项研究中,使用羟乙基淀粉(HES)和亚油酸作为原料制备两亲性LHES聚合物。分析了LHES聚合物中亚油酸基团的含量和取代度。LHES聚合物用于制造携带亚油酸修饰的小檗碱衍生物(L-BBR)的LHES-B纳米颗粒。LHES-B纳米粒显示出高的载药率(29%),在酸性pH条件下(pH=4.5)能快速释放L-BBR。生物学研究表明，LHES-B纳米颗粒显着抑制HepG2细胞的增殖，并表现出比L-BBR更高的细胞毒性。在转基因Tg（fabp10：rtTA2s-M2;TRE2：EGFP-krasv12）斑马鱼模型中，LHES-B纳米颗粒明显抑制krasv12癌基因的表达。这些结果表明，LHES载体可以提高L-BBR的抗癌活性，合成的LHES-B纳米粒子显示出作为抗癌药物的巨大潜力。
