title: Development of a Hypoxic Radiosensitizer-Prodrug Liposome Delivery DNA Repair Inhibitor Dbait Combination with Radiotherapy for Glioma Therapy.
abstract: Gliomas are highly radioresistant tumors, mainly due to hypoxia in the core region of the gliomas and efficient DNA double-strand break repair. However, the design of a radiosensitizer incorporating the two above mechanisms is difficult and has rarely been reported. Thus, this study develops a hypoxic radiosensitizer-prodrug liposome (MLP) to deliver the DNA repair inhibitor Dbait (MLP/Dbait) to achieve the simultaneous entry of radiosensitizers with two different mechanisms into the glioma. MLP/Dbait effectively sensitizes glioma cells to X-ray radiotherapy (RT). Histological and microscopic examinations of dissected brain tissue confirm that MLP effectively delivers Dbait into the glioma. Furthermore, the combination of MLP/Dbait with RT significantly inhibits growth of the glioma, as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a Dbait delivery system to enhance the effect of RT on glioma, owing to the synergistic effects of the two different radiosensitizers.
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Cancer Institute of Xuzhou Medical University, Xuzhou, 221002, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hua
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, 221116, P. R. China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Cancer Institute of Xuzhou Medical University, Xuzhou, 221002, P. R. China.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.|Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000860:Hypoxia / Q000473:pathology*; D008081:Liposomes; D008813:Mice, Inbred ICR; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D066244:Proton Magnetic Resonance Spectroscopy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011355:Prodrugs; D011838:Radiation-Sensitizing Agents
keywords: Dbait; glioma; hypoxic radiosensitizer-prodrug; radiotherapy