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