Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human lung cancer

作者：Wu, Jintian; Deng, Chao^*; Meng, Fenghua; Zhang, Jian; Sun, Huanli; Zhong, Zhiyuan^*

来源：Journal of Controlled Release, 2017, 259: 76-82.

DOI：10.1016/j.jconrel.2016.12.024

• PLGA nanoparticles
• Docetaxel
• Coating
• Nanomedicine
• Lung cancer

PLGA nanotherapeutics though representing a most promising platform for targeted cancer therapy are confronted with low stability and insufficient tumor cell uptake. Here, we report that hyaluronic acid (HA) coated PLGA nanoparticulate docetaxel (DTX-HPLGA) is particularly robust and can effectively target and suppress orthotopic human lung cancer. DTX-HPLGA was easily prepared with a small size of 154 nm and negative surface charge of - 22.7 mV by nanoprecipitation and covalent coating with HA. DTX-HPLGA displayed a low IC50 of 0.91 mu g/mL in CD44+ A549 cells and a prolonged elimination half-life of 4.13 h in nude mice. Interestingly, DTX-HPLGA demonstrated 4.4-fold higher accumulation in the cancerous lung than free DTX, reaching a remarkable level of 13.7 % ID/g at 8 h post-injection, in orthotopic human A549 lung cancer-bearing mice. Accordingly, DTX-HPLGA exhibited significantly better inhibition of tumor growth than free DTX, leading to healthy mice growth and markedly improved survival time. DTX-HPLGA with easy fabrication, excellent stability and tumor accumulation, effective tumor suppression, and low side effects is of particular interest for targeted chemotherapy of lung cancers.

• 出版日期2017-8-10
• 单位苏州大学