The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma
The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma
复制标题
负载多西紫杉醇的固体脂质纳米粒靶向肝细胞癌的性能。
DOI：
10.1016/j.biomaterials.2008.09.014
复制
发表时间：
2009-01-01
期刊：
影响因子：
14
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Xu, Zhenghong;Chen, Lingli;Li, Yaping
人类肝细胞癌（HCC）是世界范围内的主要死亡原因之一。以细胞、组织或疾病特异性方式靶向摄取治疗剂代表了治疗HCC的潜在技术。以半乳糖化二油酰磷脂酰乙醇胺为原料，设计并制备了一种新的紫杉醇肝癌靶向固体脂质纳米粒（tSLN）。研究了tSLN的细胞毒性、细胞摄取、亚细胞定位、体内毒性、治疗效果、生物分布和组织学。tSLN的粒径约为120 nM，包封率> 90%，第一天内爆发效应较低，体外持续释放29天。tSLN对肝细胞癌细胞系BEL7402的细胞毒性上级于泰索帝（R）和非靶向SLN（nSLN）。与泰索帝（R）或nSLN相比，tSLN在荷肝癌的小鼠模型中也显示出更好的耐受性和抗肿瘤功效。细胞摄取和生物分布研究表明，tSLNs的抗肿瘤作用与其在肿瘤组织中的蓄积增加和肝癌细胞的摄取增加有关。组织学证明tSLN对健康肝脏和纤维化肝脏均无不利影响。这些结果表明，这种靶向多西紫杉醇纳米载体可以增强其体内抗肿瘤作用，并且全身毒性较低，用于治疗局部晚期和转移性肝癌。(c)2008爱思唯尔有限公司保留所有权利。
Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. Targeted uptake of therapeutic agent in the cell-, tissue- or disease-specific manner represents a potential technology for the treatment of HCC. A new docetaxel-loaded hepatoma-targeted solid lipid nanoparticle (tSLN) was designed and prepared with galactosylated dioleoylphosphatidyl ethanolamine. The cellular cytotoxicity, cellular uptake, subcellular localization, in vivo toxicity, therapeutic effect, biodistribution and histology of tSLNs were investigated, The tSLNs showed the particle size about 120 nM with encapsulation efficiency > 90%, a low burst effect within the first day and a sustained release for the next 29 days in vitro. Cytotoxicity of tSLNs against hepatocellular carcinoma cell line BEL7402 was superior to Taxotere (R) and non-targeted SLNs (nSLNs). The tSLNs also showed better tolerant and antitumor efficacy in murine model bearing hepatoma compared with Taxotere (R) or nSLNs. The studies on cellular uptake and biodistribution indicated that the better antitumor efficacy of tSLNs was attributed to both the increased accumulation of drug in tumor and more cellular uptake by hepatoma cells. The histology demonstrated that tSLNs had no detrimental effect on both healthy liver and liver with fibrosis. These results implied that this targeted nanocarrier of docetaxel could enhance its antitumor effect in vivo with low systemic toxicity for the treatment of locally advanced and metastatic HCC. (c) 2008 Elsevier Ltd. All rights reserved.