Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Biomacromolecules. 2010 Sep 13;11(9):2422-31. doi: 10.1021/bm1005992.
Although surgery offers the only hope of cure for hepatocellular carcinoma (HCC), patients with inoperable or metastatic disease have a dismal prognosis. Therefore, there is an urgent need for new and effective treatment strategies. Polymeric micelles composed of drug conjugated to a diblock copolymer have attracted great interest for clinical administration of anticancer drugs. In this work, characteristics and cytotoxicity of doxorubicin-poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) (DOX-PLGA-PEG) micelle and its targeted micelle decorated with bivalent fragment HAb18 F(ab')(2) for HCC were studied. These micelles possessed spherical morphology and higher loading efficiency. Cellular uptake and accumulation in tumor tissue of micelles was observed. The accumulation of the targeted micelles depends on dual effects of passive and active targeting. The drug-loading micelles showed cytotoxicity on tumor cells in vitro and in vivo. The targeted micelles resulted in significant improvement in therapeutic response. These results suggest that the novel micelles could be a promising candidate with excellent therapeutic efficacy for targeting the drugs to cancer cells.
虽然手术为肝细胞癌（HCC）提供了唯一的治愈希望，但对于无法手术或转移性疾病的患者，预后极差。因此，迫切需要新的、有效的治疗策略。由药物偶联到二嵌段共聚物的聚合物胶束在临床抗癌药物给药方面引起了极大的兴趣。在这项工作中，研究了阿霉素-聚（D，L-乳酸-共-乙醇酸）-聚乙二醇（DOX-PLGA-PEG）胶束及其靶向胶束的特性和细胞毒性，该靶向胶束用二价片段 HAb18 F(ab')(2)进行了修饰，用于治疗 HCC。这些胶束具有球形形态和更高的载药效率。观察到胶束的细胞摄取和在肿瘤组织中的积累。靶向胶束的积累取决于被动和主动靶向的双重作用。载药胶束在体外和体内对肿瘤细胞显示出细胞毒性。靶向胶束显著改善了治疗反应。这些结果表明，新型胶束可能是一种很有前途的候选药物，具有优异的治疗效果，可将药物靶向癌细胞。
