Hyaluronic Acid-Modified Micelles Encapsulating Gem-C12 and HNK for Glioblastoma Multiforme Chemotherapy

作者：Liu, Xing; Li, Wenhao; Chen, Tijia; Yang, Qin; Huang, Ting; Fu, Yao; Gong, Tao^*; Zhang, Zhirong

来源：Molecular Pharmaceutics, 2018, 15(3): 1203-1214.

DOI：10.1021/acs.molpharmaceut.7b01035

• glioblastoma multiforme
• combination chemotherapy
• lauroyl-gemcitabine
• honokiol
• hyaluronic acid
• CD44

Glioblastoma multiforme (GBM), a prevalent brain cancer with high mortality, is resistant to the conventional single-agent chemotherapy. In this study, we employed a combination chemotherapy strategy to inhibit GBM growth and addressed its possible beneficial effects. The synergistic effect of lauroyl-gemcitabine (Gem-C-12) and honokiol (HNK) was first tested and optimized using U87 cells in vitro. Then, the hyaluronic acid-grafted micelles (HA-M), encapsulating the optimal mole ratio (1:1) of Gem-C-12 and HNK, were prepared and characterized. Cell-based studies demonstrated that HA-M could be transported into cells by a CD44 receptor-mediated endocytosis, which could penetrate deeper into tumor spheroids and enhance the cytotoxicity of payloads to glioma cells. In vivo, drug-loaded HA-M significantly increased the survival rate of mice bearing orthotopic xenograft GBM compared with the negative control (1.85-fold). Immunohistochemical analysis indicated that the enhanced efficacy of HA-M was attributed to the stronger inhibition of glioma proliferation and induction of apoptosis. Altogether, our findings showed advantages of combination chemotherapy of GBM using HA-grafted micelles.

• 出版日期2018-3
• 单位四川大学