Department of Materials Science and Engineering, College of Engineering and Beijing Key Laboratory for Magnetoelectric Materials and Devices, Peking University , Beijing 100871, China.
ACS Appl Mater Interfaces. 2017 Sep 20;9(37):31458-31468. doi: 10.1021/acsami.7b08969. Epub 2017 Sep 5.
Intraorgan targeting of chemical drugs at tumor tissues is essential in the treatment of solid tumors that express the same target receptor as normal tissues. Here, asialoglycoprotein receptor (ASGP-R)-targeting paclitaxel-conjugated gold nanoparticles (Gal/PTX-GNPs) are fabricated as a demonstration to realize the precise treatment of liver cancer. The enhanced biological specificity and therapeutic performance of drugs loaded on nanoparticles not only rely on the ligands on carriers for receptor recognition but are also determined by the performance of gold conjugates with designed structure. The tumor cell selectivity of the designed conjugates in liver tumor (HepG2) cells is close to six times of that incubated with control conjugates without galactose modification in liver normal (L02) cells. The drug level in tumor versus liver of Gal/PTX-GNPs is 121.0% at 8 h post injection, a 15.7-fold increase in the tumor specificity compared to that of GNPs conjugated with PTX only. This intraorgan-targeting strategy results in a considerable improvement of performance in treating both Heps heterotopic and orthotopic xenograft tumor models, which is expected to be used for the enhanced antitumor efficacy and reduced hepatotoxicity in liver cancer treatment.
在治疗表达与正常组织相同靶受体的实体瘤时，将化学药物靶向递送到肿瘤组织内对于实现这一目标至关重要。在这里，我们制备了作为范例的通过去唾液酸糖蛋白受体（ASGP-R）靶向的紫杉醇偶联金纳米颗粒（Gal/PTX-GNPs），以实现肝癌的精准治疗。载药纳米颗粒的增强的生物特异性和治疗性能不仅依赖于载体上配体的受体识别，而且还取决于具有设计结构的金缀合物的性能。设计的缀合物在肝癌（HepG2）细胞中的肿瘤细胞选择性接近未经半乳糖修饰的对照缀合物在正常肝（L02）细胞中的 6 倍。与仅用 PTX 偶联的 GNPs 相比，Gal/PTX-GNPs 在注射后 8 小时时肿瘤与肝脏的药物水平为 121.0%，肿瘤特异性提高了 15.7 倍。这种靶向器官内的策略显著提高了治疗异位和原位异种移植肿瘤模型的疗效，有望提高肝癌治疗的抗肿瘤疗效并降低肝毒性。
