Abstract
Combination chemotherapy is an important protocol in glioma therapy and honokiol shows synergistic anticancer effects with doxorubicin. In this paper, honokiol (HK) and doxorubicin (Dox) co-loaded Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) nanoparticles were prepared with a assembly method. The particle size (about 34 nm), morphology, X-ray Powder Diffraction (XRD), in vitro release profile, cytotoxicity and cell proliferation effects were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PCL nanoparticles simultaneously, and could be released from the micelles in an extended period in vitro. In addition, honokiol and doxorubicin loaded in MPEG-PCL nanoparticles could efficiently suppress glioma cell proliferation and induce cell apoptosis in vitro. Furthermore, Dox-HK-MPEG-PCL micelles inhibited glioma growth more significantly than Dox-MPEG-PCL and HK-MPEG-PCL in both nude mice and zebrafish tumor models. Immunohistochemical analysis indicated that DOX-HK-MPEG-PCL micelles improved Dox’s anti-tumor effect by enhancing tumor cell apoptosis, suppressing tumor cell proliferation, and inhibiting angiogenesis. Our data suggest that Dox-HK-MPEG-PCL micelles have the potential to be applied clinically in glioma therapy.
Highlights
(epithelial-mesenchymal transition) in breast cancer[17]
Our results suggest that DOX-HK-M nano-micelles provide a novel formulation of HK and DOX, with promising applications in glioma therapy
The organic phase was evaporated in a rotary evaporator under reduced pressure, and subsequent addition of water formed the core-shell structured HK/MPEG-PCL nano-micelles with core-encapsulated HK
Summary
(epithelial-mesenchymal transition) in breast cancer[17]. In addition, HK showed synergistic antitumor effects when combined with chemotherapy[18]. The hydrophobic PCL segments pack together to form the core which serves as a potential nanocontainer of hydrophobic drugs, while the outer hydrophilic PEG region serves as a stabilizing shell; the encapsulation of hydrophobic drugs into the core-shell nanostructure can render them completely dispersible in solution[26]. As such, these micelles provide an attractive method to make nanovector-based formulations for hydrophobic drugs. Our results suggest that DOX-HK-M nano-micelles provide a novel formulation of HK and DOX, with promising applications in glioma therapy
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