Hyaluronic Acid-Modified Micelles Encapsulating Gem‑C<sub>12</sub> and HNK for Glioblastoma Multiforme Chemotherapy Xing Liu Wenhao Li Tijia Chen Qin Yang Ting Huang Yao Fu Tao Gong Zhirong Zhang 10.1021/acs.molpharmaceut.7b01035.s001 https://acs.figshare.com/articles/journal_contribution/Hyaluronic_Acid-Modified_Micelles_Encapsulating_Gem_C_sub_12_sub_and_HNK_for_Glioblastoma_Multiforme_Chemotherapy/5877384 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<sub>12</sub>) 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<sub>12</sub> 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. 2018-02-04 00:00:00 orthotopic xenograft GBM glioma Glioblastoma Multiforme Chemotherapy Glioblastoma multiforme micelle HNK combination chemotherapy strategy Gem-C 12 CD 44 receptor-mediated endocytosis HA-M U 87 cells