Medium-chain triglyceride-stabilized docetaxel-loaded HSA nanoparticles effectively inhibited metastatic non-small cell lung cancer.

ABSTRACT

Metastatic non-small cell lung cancer (NSCLC) is refractory with a very poor prognosis. Docetaxel (DTX) injection (Taxotere®) has been approved for the treatment of locally advanced or metastatic NSCLC. However, its clinical application is restricted by severe adverse effects and non-selective tissue distribution. In this study, we successfully developed DTX-loaded human serum albumin (HSA) nanoparticles (DNPs) with modified Nab technology, by introducing medium-chain triglyceride (MCT) as a stabilizer. The optimized formulation had a particle size of approximately 130 nm and a favorable stabilization time of more than 24 h. DNPs dissociated in circulation in a concentration-dependent manner and slowly released DTX. Compared with DTX injection, DNPs were more effectively taken up by NSCLC cells, thus exerting stronger inhibitory effects on their proliferation, adhesion, migration, and invasion. In addition, DNPs showed prolonged blood retention and increased tumor accumulation relative to DTX injection. Ultimately, DNPs produced more potent inhibitory effects on primary or metastatic tumor foci than DTX injections but caused markedly lower organ toxicity and hematotoxicity. Overall, these results support that DNPs hold great potential for the treatment of metastatic NSCLC in clinical.