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

Jintian Wu, Chao Deng ^*（邓超）, Fenghua Meng, Jian Zhang, Huanli Sun, Zhiyuan Zhong ^*（钟志远）

Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China

Journal of Controlled Release259 (2017) 76–82

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 nanoparticulatedocetaxel (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 μg/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.

链接：http://www.sciencedirect.com/science/article/pii/S016836591631272X