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Adv Healthc Mater. 2017 Jun;6(12). doi: 10.1002/adhm.201601377. Epub 2017 Mar 30.

Development of a Hypoxic Radiosensitizer-Prodrug Liposome Delivery DNA Repair Inhibitor Dbait Combination with Radiotherapy for Glioma Therapy.

Liu H1,2, Cai Y1,2, Zhang Y1,2, Xie Y1,2, Qiu H3,4, Hua L1,2, Liu X1,2, Li Y5, Lu J6, Zhang L3,4, Yu R1,2.

Author information

1
Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
2
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, P. R. China.
3
Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
4
Cancer Institute of Xuzhou Medical University, Xuzhou, 221002, P. R. China.
5
School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, 221116, P. R. China.
6
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, P. R. China.

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.

KEYWORDS:

Dbait; glioma; hypoxic radiosensitizer-prodrug; radiotherapy

PMID:
28371526
DOI:
10.1002/adhm.201601377
[Indexed for MEDLINE]

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