Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
J Control Release. 2017 Aug 10;259:76-82. doi: 10.1016/j.jconrel.2016.12.024. Epub 2016 Dec 24.
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 IC 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.
PLGA 纳米治疗药物尽管是靶向癌症治疗最有前途的平台，但面临着低稳定性和肿瘤细胞摄取不足的问题。在这里，我们报告称，透明质酸（HA）包覆的 PLGA 纳米载体制备的多西紫杉醇（DTX-HPLGA）具有特别的稳定性，能够有效靶向并抑制原位人肺癌。通过纳米沉淀和 HA 的共价包覆，很容易制备出粒径为 154nm、表面负电荷为-22.7mV 的 DTX-HPLGA。在 CD44+ A549 细胞中，DTX-HPLGA 的 IC50 低至 0.91μg/mL，在裸鼠体内的消除半衰期延长至 4.13h。有趣的是，与游离 DTX 相比，DTX-HPLGA 在肺癌中的积累增加了 4.4 倍，在荷人原位 A549 肺癌的裸鼠中，8h 时达到了 13.7%ID/g 的显著水平。因此，DTX-HPLGA 对肿瘤生长的抑制作用明显优于游离 DTX，使小鼠健康生长，存活时间显著延长。DTX-HPLGA 具有易于制备、优异的稳定性和肿瘤积累、有效的肿瘤抑制作用以及较低的副作用，特别适合肺癌的靶向化疗。
