Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152# Luoyu Road, Wuhan, Hubei 430079, PR China.
Int J Biol Macromol. 2010 Mar 1;46(2):245-9. doi: 10.1016/j.ijbiomac.2009.11.008. Epub 2009 Dec 1.
Xyloglucan was grafted with the doxorubicin (DOX) and galactosamine, a terminal moiety that can be used to target polymeric conjugates to liver hepatocytes. The content of the DOX was over 5% (wt) in the conjugate. The polymeric drug assisted to form nanoparticle drug delivery systems (nanoDDSs) with an average size of 142 nm in diameter when combined with an excess amount of deprotonated doxorubicin in an aqueous phase. A loading content of doxorubicin is as high as 23.8% in the nanoDDS. In an in vitro cytotoxicity experiment, the novel nanoDDS has similar cytotoxicity as free DOX against HepG2 cells. In contrast, for the incubation with HeLa cells of the novel nanoDDS, there was no significant cytotoxicity change. In a human tumor xenograft nude mouse model, the novel nanoDDS generated higher therapeutic effect than non-targeted doxorubicin nanoparticles or free doxorubicin. Together, these results suggest that novel nanoDDS, which has improved transfection efficiency and hepatocyte specificity, may be useful for tumor therapy.
木葡聚糖与阿霉素（DOX）和半乳糖胺接枝，半乳糖胺是一种末端部分，可以将聚合物缀合物靶向到肝实质细胞。缀合物中 DOX 的含量超过 5%（wt）。当与过量带负电荷的阿霉素在水相中结合时，该聚合物药物有助于形成平均直径为 142nm 的纳米粒药物递送系统（nanoDDS）。纳米 DDS 中的阿霉素载药量高达 23.8%。在体外细胞毒性实验中，新型 nanoDDS 对 HepG2 细胞的细胞毒性与游离 DOX 相似。相比之下，对于新型 nanoDDS 与 HeLa 细胞的孵育，没有明显的细胞毒性变化。在人肿瘤异种移植裸鼠模型中，新型 nanoDDS 比非靶向阿霉素纳米粒或游离阿霉素产生更高的治疗效果。总之，这些结果表明，新型 nanoDDS 具有提高的转染效率和肝实质细胞特异性，可能对肿瘤治疗有用。
