Application of luteolin nanomicelles anti-glioma effect with improvement in vitro and in vivo

Glioblastoma multiforme (GBM) is one of the most common and malignant tumor. Luteolin, a polyphenolic compound, has been proposed to have anti-tumor activity against various cancers. However, the greatest obstacle in the administration of luteolin is its hydrophobicity as well as the low oral bioavailability. In this study, we formulated luteolin-loaded MPEG-PCL (Luteolin/MPEG-PCL) micelles aiming to improve its solubility in aqueous solution and investigate the anti-tumor effect on glioma in vitro and in vivo. The spherical Luteolin/MPEG-PCL micelles were completely dispersible in normal saline and could release luteolin in a sustained manner in vitro. We demonstrated that Luteolin/MPEG-PCL micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in C6 and U87 cells than free luteolin in vitro. The immunohistochemical study revealed that Luteolin/MPEG-PCL micelles induced more glioma cell apoptosis than free luteolin and inhibited neovascularization in tumor tissues. The Pro-caspase9 and Bcl-2 down-regulation and cleaved-caspase9 and Bax up-regulation suggested that luteolin induced apoptosis via the mitochondrial pathway in vitro. What is more, we found the drug could cumulated much more in the nano-drug group than free drug group through imaging in vivo. In conclusion, the Luteolin/MPEG-PCL micelles have the potential clinical application in glioma chemotherapy.