title: Enhancing the anti-glioma therapy of doxorubicin by honokiol with biodegradable self-assembling micelles through multiple evaluations.
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.
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.|Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, Connecticut, 06520, USA.|Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Guangya
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.|Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.|Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004357:Drug Synergism; D006801:Humans; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004317:Doxorubicin; D004337:Drug Carriers; D017705:Lignans; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols