Key Laboratory of Pesticide and Chemical Biology (Ministry of Education), College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
Ann Biomed Eng. 2011 Sep;39(9):2456-65. doi: 10.1007/s10439-011-0333-2. Epub 2011 Jun 24.
Intracellular targeted conjugates of xyloglucan and mitomycin C (MMC) were synthesized with a lysosomally degradable peptide spacer and galactosamine, a terminal moiety that can be used to target polymeric conjugates to hepatoma. The content of the MMC was about 3.5% (mol) in this conjugate. In an in vitro cytotoxicity experiment, the targeted prodrugs have higher cytotoxicity than free MMC against the drug resistant HepG2 cells. In a human tumor xenograft nude mouse model, the targeted prodrugs generated higher therapeutic effect than non-targeted prodrugs or free MMC. Together, these results suggest that targeted prodrugs, which have improved transfer efficiency and hepatocyte specificity, may be useful for the reversion of drug resistant HepG2 cells.
木葡聚糖和丝裂霉素 C（MMC）的细胞内靶向缀合物与溶酶体可降解肽间隔物和半乳糖胺合成，半乳糖胺是一种末端部分，可以将聚合物缀合物靶向肝癌。该缀合物中 MMC 的含量约为 3.5%（摩尔）。在体外细胞毒性实验中，与游离 MMC 相比，靶向前药对耐药 HepG2 细胞具有更高的细胞毒性。在人肿瘤异种移植裸鼠模型中，靶向前药比非靶向前药或游离 MMC 产生更高的治疗效果。总之，这些结果表明，具有提高的转移效率和肝细胞特异性的靶向前药可能有助于逆转耐药 HepG2 细胞。
