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Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human 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 154nm and negative surface charge of -22.7mV by nanoprecipitation and covalent coating with HA. DTX-HPLGA displayed a low IC50 of 0.91μg/mL in CD44+ A549 cells and a prolonged elimination half-life of 4.13h 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 8h 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.

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